<i>Background</i>. Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML. <i>Methods</i>. Patients with Ph+ CML in the chronic phase (<i>n</i> = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR. <i>Results</i>. JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR. <i>Conclusions</i>. Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.

Indra Wijaya

Muhammad H. Bashari

Lelani Reniarti

Anita Rahmawati

Rully M. A. Roesli

JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib

<i>Introduction</i>. Metaplastic breast carcinoma (MBC) is a rare subgroup of breast neoplasms associated with adverse outcomes because of its aggressive nature. Typically, MBCs show triple-negative hormone receptor (HR) status. Determining the HR status of breast cancer is an integral part because it is an important prognostic factor and helps in the treatment course of the disease. This study aimed to determine the HR status of MBC, its significance, and its association with various clinicopathological parameters. <i>Methods</i>. This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital. A total of 140 biopsy-proven cases of MBC were enrolled in the study. Clinical and pathological data were retrieved from the institutes’ archives. Immunohistochemical studies were conducted to determine the estrogen receptor (ER) and progesterone receptor (PR) status. <i>Results</i>. The mean age of MBC in our population was found to be 52.18 ± 12.19 years. The HR positivity rate in our population was found to be 32.9%. A significant association was found between HR status and tumor laterality, tumor size, tumor grade, tumor stage, and recurrence. ER/PR-negative MBCs were most probably associated with higher grade and higher tumor stage and were larger in size (6.62 ± 3.43 cm) than ER/PR-positive MBCs (4.20 ± 1.88 cm). Moreover, ER/PR-positive MBCs showed a higher recurrence rate than ER/PR-negative MBCs (43.5% vs. 25.5%, respectively). No statistically significant relationship was found between HR status and patient age, histological subtype, or survival rate. <i>Conclusion</i>. MBC is a rare breast neoplasm. MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis.

Atif Ali Hashmi

Bakhtawar Allauddin Mallick

Khushbakht Rashid

Umair Arshad Malik

Shamail Zia

Fazail Zia

Muhammad Irfan

Significance of Estrogen/Progesterone Receptor Expression in Metaplastic Breast Carcinoma

<i>Introduction</i>. Lung cancer ranks first among malignant tumors worldwide and is a leading cause of cancer-related mortality in both men and women. Combining tumor marker testing is a strategy to screen individuals at high risk of pulmonary cancer and minimize pulmonary cancer mortality. Therefore, tumor marker screening is crucial. In this study, we analyzed combinations of tumor markers for lung cancer screening using receiver operating characteristic (ROC) curve analysis. <i>Methods</i>. A retrospective descriptive study was conducted on patients diagnosed with lung cancer, as well as healthy and benign lung diseases, using data from the China Huludao Central Hospital database between January 2016 and July 2022. The <i>t</i>-test and ROC curve were utilized to assess the effectiveness of individual tumor marker and the combination of multiple tumor markers. Tumor markers are molecular products metabolized and secreted by tumor tissues, characterized by cells or body fluids. They serve as indicators of tumor stage and grading, monitor treatment response, and predict recurrence. <i>Results</i>. In this study, 267 healthy participants, 385 patients with benign lesions, and 296 patients with lung cancer underwent tumor marker screening. The sensitivity of five tumor markers—CEA, CYFRA21-1, NSE, pro-GRP, and CA125—was found to be <55%. This study revealed that a single tumor marker had limited value in lung cancer screening. However, combining two or more markers yielded varying area under the curves (AUC), with no significant impact on screening accuracy. The combination of CEA + CA125 demonstrated the highest accuracy for lung cancer screening in healthy participants. At a cutoff of 0.447 for CEA + CA125, the combination showed a sensitivity of 0.676 and specificity of 0.846 for lung cancer screening. Conversely, for patients with benign lung lesions, the optimal combination was CEA + NSE, with a cutoff of 0.393, yielding a sensitivity of 0.645 and specificity of 0.766 for lung cancer screening. <i>Conclusion</i>. The five tumor markers—CEA, CA125, CY211, NSE, GRP—show promising results in screening healthy individuals and patients with lung cancer. However, only CEA, NSE, and GRP effectively differentiate patients with benign lung lesions from those with lung cancer. A single tumor marker has limited utility in detecting and screening for lung cancer and should be combined with other tumor markers. CEA + CA125 emerges as a superior tumor marker for distinguishing healthy individuals from those with lung cancer, whereas the CEA + NSE combination is more effective in identifying tumor markers in patients with benign lung lesions and lung cancer.

Xiaofeng Dou

Jiachen Lu

Yingying Yu

Yaohui Yi

Ling Zhou

Determination of Tumor Marker Screening for Lung Cancer Using ROC Curves

<i>Objective</i>. Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the expression of plasma microRNA-320c (miR-320c) in patients with knee OA and to explore the clinical value and potential mechanism of miR-320c in knee OA. <i>Methods</i>. Forty knee OA patients and 20 healthy controls were enrolled. The levels of plasma miR-320c and plasma inflammatory cytokines were measured by real-time PCR or ELISA. Correlations of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and cytokine levels with the miR-320c expression level were evaluated by Pearson correlation analysis. Then, a receiver operating characteristic (ROC) curve was drawn to analyse the diagnostic value of miR-320c in OA. Finally, the interaction of miR-320c and cAMP responsive element binding protein 5 (CREB5) was determined using a luciferase reporter assay, and the effect of CREB5 on the cAMP pathway was assessed. <i>Results</i>. The expression level of plasma miR-320c was significantly higher in OA patients than in healthy controls (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M1" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.921pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 21.921 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>).</span></span> The increased plasma miR-320c level was positively correlated with the WOMAC score (<i>r</i> = 0.796, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M2" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.185pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 28.185 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,46.464,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>)</span></span> and the plasma interleukin (IL)-1<i>β</i> (<i>r</i> = 0.814, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.185pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 28.185 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,46.464,0)"><use xlink:href="#g113-50"/></g></svg>)</span></span> and IL-6 (<i>r</i> = 0.695, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.185pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 28.185 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,46.464,0)"><use xlink:href="#g113-50"/></g></svg>)</span></span> levels in patients with OA. ROC curve analysis demonstrated the relatively high diagnostic accuracy of plasma miR-320c for OA. Furthermore, the luciferase reporter assay results showed that miR-320c regulates CREB5 expression by binding to the CREB5 3′-untranslated region. Moreover, suppression of CREB5 significantly reduced the expression levels of c-fos and c-jun. <i>Conclusion</i>. Our results indicate that plasma miR-320c may serve as a potential novel predictor of the severity of knee OA and that miR-320c may play an important role in the pathogenesis of OA through inhibiting the cAMP pathway by targeting CREB5.

Rongwei Zhou

Like Zhao

Qian Wang

Yongjing Cheng

Miao Song

Cibo Huang

Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes

<i>Objective</i>. The present article aims to comprehensively review the existing literature on superoxide dismutase (SOD) levels, an antioxidant enzyme, in oral cancer. <i>Method</i>. An extensive literature search was conducted across various databases, including PubMed, Wiley Online Library, Science Direct, and Cross Reference, spanning 1998–2023. At the outset, 1,177 articles were initially identified, and 907 studies were excluded due to irrelevance or duplication of the research question. Subsequently, 270 articles underwent screening evaluation, resulting in the selection of 85 articles meeting the inclusion criteria. Following this, 68 articles underwent a full-text comprehensive assessment, and ultimately, 39 were chosen for data extraction. The risk of bias in the designated articles was assessed using the Newcastle–Ottawa Scale. Finally, 13 studies were meticulously selected, offering consistent data for the ensuing meta-analysis. Meta-analysis was executed using comprehensive meta-analysis (CMA) version 3 software (Bio Stat Inc., Englewood, NJ, USA). The meta-analysis findings revealed a statistically significant decrease in SOD levels in both erythrocyte samples (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M1" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>)</span></span> and tissue samples (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M2" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>)</span></span> among individuals with oral cancer (OSCC) compared to the normal control group. Conversely, the analysis of three studies on salivary samples demonstrated a significant increase (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-54"/></g></svg>)</span></span> in SOD levels in the oral cancer group compared to the healthy controls. <i>Conclusion</i>. This systematic review underscores a statistically significant decline in SOD levels observed across diverse bio-samples in individuals with oral cancer, indicating an excess of oxidative stress (OS). Additional research is needed to delve into the relationship between SOD levels and clinic–pathological prognostic markers within the oral cancer cohort. Such investigations have the potential to significantly contribute to the development of prognostic tools grounded in OS, thereby guiding strategies for treatment planning.

Khadijah Mohideen

Krithika Chandrasekaran

Kareema M

Jeyanthikumari T

Safal Dhungel

Snehashish Ghosh

Assessment of Antioxidant Enzyme Superoxide Dismutase (SOD) in Oral Cancer: Systematic Review and Meta-Analysis

Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.

Somayeh Igder

Mozhdeh Zamani

Shima Fakher

Morvarid Siri

Hassan Ashktorab

Negar Azarpira

Pooneh Mokarram

Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value

<i>Objective</i>. The neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer. <i>Methods</i>. This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves. <i>Results</i>. Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38–51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14–7.71) vs. 0.92 (0.67–1.09), <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M1" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.185pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 28.185 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,46.464,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>).</span></span> Similarly, the PLR was higher among cases than controls (237.5 (177.8–361.6) vs. 123.6 (100.6–155.4), <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M2" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%–98.4%), 100% (95% CI: 96.2%–100%), and 0.94 (95% CI: 0.85–1.00, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.185pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 28.185 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,46.464,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%–92.7%), 87.2% (95% CI: 78.8%–93.2%), and 0.81 (95% CI: 0.70–0.93, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.148pt" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 21.148 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,13.517,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.185pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="24.730183800000002 -8.34882 28.185 11.7782"><g transform="matrix(.013,0,0,-0.013,24.78,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,31.02,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,33.984,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,40.224,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,46.464,0)"><use xlink:href="#g113-50"/></g></svg>)</span></span> at a cutoff of 196.3. <i>Conclusion</i>. The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology.

Joseph Baruch Baluku

Sharon Namiiro

Brenda Namanda

Martin Nabwana

Irene Andia-Biraro

William Worodria

Robert Salata

Sayoki Mfinanga

Stanton Gerson

Bruce Kirenga

Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios in Distinguishing Lung Cancer in People with HIV

Genetic variations in urate transporters play a significant role in determining human urate levels and have been implicated in developing hyperuricemia or gout. Polymorphism in the key urate transporters, such as ABCG2, URAT1, or GLUT9 was well-documented in the literature. Therefore in this study, our objective was to determine the frequency and effect of rare nonsynonymous allelic variants of <i>SLC22A11</i>, <i>SLC22A13</i>, and <i>SLC17A1</i> on urate transport. In a cohort of 150 Czech patients with primary hyperuricemia and gout, we examined all coding regions and exon–intron boundaries of <i>SLC22A11</i>, <i>SLC22A13</i>, and <i>SLC17A1</i> using PCR amplification and Sanger sequencing. For comparison, we used a control group consisting of 115 normouricemic subjects. To examine the effects of the rare allelic nonsynonymous variants on the expression, intracellular processing, and urate transporter protein function, we performed a functional characterization using the HEK293A cell line, immunoblotting, fluorescent microscopy, and site directed mutagenesis for preparing variants <i>in vitro</i>. Variants p.V202M (rs201209258), p.R343L (rs75933978), and p.P519L (rs144573306) were identified in the <i>SLC22A11</i> gene (OAT4 transporter); variants p.R16H (rs72542450), and p.R102H (rs113229654) in the <i>SLC22A13</i> gene (OAT10 transporter); and the p.W75C variant in the <i>SLC17A1</i> gene (NPT1 transporter). All variants minimally affected protein levels and cytoplasmic/plasma membrane localization. The functional <i>in vitro</i> assay revealed that contrary to the native proteins, variants p.P519L in OAT4 (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M1" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-93" d="M531 71V127L115 310L531 494V550L57 335V285L531 71ZM531 -40V10H57V-40H531Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.921pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 21.921 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>),</span></span> p.R16H in OAT10 (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M2" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-93"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.921pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 21.921 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-54"/></g></svg>),</span></span> and p.W75C in the NPT1 transporter (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-93"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.921pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 21.921 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>)</span></span> significantly limited urate transport activity. Our findings contribute to a better understanding of (1) the risk of urate transporter-related hyperuricemia/gout and (2) uric acid handling in the kidneys.

Jiří Vávra

Kateřina Pavelcová

Jana Mašínová

Lenka Hasíková

Eliška Bubeníková

Aneta Urbanová

Andrea Mančíková

Blanka Stibůrková

Examining the Association of Rare Allelic Variants in Urate Transporters <i>SLC22A11</i>, <i>SLC22A13</i>, and <i>SLC17A1</i> with Hyperuricemia and Gout

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<p><em>Disease Markers</em> publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.</p>


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<p>Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.</p>


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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

Disease Markers