Disease Markers
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Acceptance rate22%
Submission to final decision61 days
Acceptance to publication23 days
CiteScore4.700
Journal Citation Indicator0.720
Impact Factor3.464

Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms

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 Journal profile

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.

 Editor spotlight

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.

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We currently have a number of Special Issues open for submission. Special Issues highlight emerging areas of research within a field, or provide a venue for a deeper investigation into an existing research area.

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Research Article

Bioinformatics Analysis Identifies ASCL1 as the Key Transcription Factor in Hepatocellular Carcinoma Progression

Object. To identify and explore the key transcription factors in hepatocellular carcinoma (HCC) progression. Methods. Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells. Results. Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells. Conclusion. This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.

Research Article

Tanshinone IIA Inhibits Triple-Negative Breast Cancer Cells MDA-MB-231 via G Protein-Coupled Estrogen Receptor- (GPER-) Dependent Signaling Pathway

Due to the lack of classic estrogen receptors, there has been a shortage of targeted therapy for triple-negative breast cancer (TNBC), resulting in a poor prognosis. However, the newly discovered G protein-coupled estrogen receptor (GPER) has been found to be expressed in TNBC cells. Salvia miltiorrhiza (Danshen) is an essential Chinese medicine for gynecological disorders, and its component tanshinone IIA (Tan IIA) exerts an anticancer effect. Therefore, this study attempted to investigate whether GPER is involved in the inhibitory effect of Tan IIA on TNBC. We applied various databases and GO pathway analysis to predict the possible mechanism of Tan IIA. We identified 39 overlapping targets, including c-Jun, c-Fos, and caspase-3, and enriched cell cycle-related pathways. Next, we demonstrated the strong binding ability of Tan IIA to GPER by molecular docking assay. In the subsequent validation tests, Cell Counting Kit-8 (CCK8) assay showed that Tan IIA inhibited proliferation of MDA-MB-231 cells time and dose dependently without affecting normal cells. Using Transwell plate, flow cytometry, and Western blot assays, we showed that Tan IIA inhibited migration and induced apoptosis of MDA-MB-231 dose dependently. Importantly, protein expressions of GPER, epidermal growth factor receptor (EGFR), extracellular regulated protein kinases (ERK), c-Fos, and c-Jun were all decreased by Tan IIA dose dependently. Administration of GPER inhibitor partly abolished these effects. Furthermore, nuclear translocation of c-Fos and c-Jun as well as cell cycle-related proteins was downregulated by Tan IIA dose dependently. In summary, Tan IIA could inhibit the proliferation and migration of MDA-MB-231 cells and induce apoptosis, and the possible mechanism may be the regulation of GPER-mediated pathways, suggesting that GPER could be a therapeutic target for TNBC.

Research Article

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment

Background. The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although numerous evidences suggest a crucial role for TREM2 in tumorigenesis of some tumors, no systematic SKCM analysis of TREM2 is available. Mehods. The relationship between TREM2 expression and diagnostic and prognostic value of SKCM patients via using The Cancer Genome Atlas (TCGA) data. The expression level of TREM2 and clinical characteristic correlation in SKCM patients were assessed by the Wilcoxon rank sum test. The cox regression methods, Kaplan-Meier (KM), and log-rank test were used to assess the impact of TREM2 expression on the overall survival (OS). Furthermore, the Gene Set Enrichment Analysis (GSEA) and TIMER were performed to evaluate the enrichment pathways and potential functions and quantify the immune cell infiltration level for TREM2 expression. Results. The TREM2 in SKCM sample expression levels was significantly higher than in normal tissues. Moreover, this expression level of TREM2 was also associated with the BMI of SKCM patients. KM overall survival analysis and OS curve displayed that a high-level TREM2 expression was significantly correlated with a better SKCM prognosis of patients as compared with a low level of TREM2 expression. The GSEA analysis also revealed that TREM2 was associated with immune functions, such as neutrophil activation. Conclusion. TREM2 played a crucial role in SKCM, which might be a prognostic biomarker and correlated with immune infifiltrates in SKCM patients.

Research Article

Construction and Validation of a Novel Cuproptosis-Related Seven-lncRNA Signature to Predict the Outcomes, Immunotherapeutic Responses, and Targeted Therapy in Patients with Clear Cell Renal Cell Carcinoma

Background. Cuproptosis was recently recognized as a novel form of cell death, linked closely to the occurrence and progression of cancer. We aimed to identify prognostic cuproptosis-related long noncoding RNAs (lncRNAs) and build a risk signature to predict the prognosis and treatment responses of clear cell renal cell carcinoma (ccRCC) in this work. Methods. LASSO–Cox regression was conducted to construct the signature based on prognostic cuproptosis-related lncRNAs (CR-lncRNAs). The signature’s reliability and sensitivity were assessed by the Kaplan-Meier survival analysis and receiver operating characteristic analysis. External validation was performed via data from the International Cancer Genome Consortium database. On the basis of CR-lncRNAs, an lncRNA-microRNA-mRNA regulatory network was created, and functional enrichment analysis was used to investigate the underlying biological roles of these genes. In addition, the relationship between the risk signature and immunotherapy and targeted therapy responses was examined. Finally, the expression levels of seven candidate lncRNAs between tumor and normal cells were compared in vitro using quantitative real-time PCR. Results. A seven-CR-lncRNA risk signature was constructed, which showed a stronger potential for survival prediction than standard clinicopathological features in patients with kidney cancer. Functional enrichment analysis showed that the CR-lncRNA risk signature was enriched in ion transport-related molecular functions as well as various immune-related biological processes. Furthermore, we discovered that individuals in the high-risk group were more likely than those in the low-risk group to respond to immunotherapy and targeted therapies with medications like sunitinib and pazopanib. Finally, quantitative real-time PCR revealed that the expression levels of seven candidate lncRNAs differed significantly between RCC and healthy kidney cells. Conclusion. In summary, we generated a CR-lncRNA risk signature that may be utilized to predict outcomes in patients with ccRCC and responsiveness to immunotherapy and targeted treatment, potentially serving as a reference for clinical personalized medicine.

Research Article

lncRNA SSTR5-AS1 Predicts Poor Prognosis and Contributes to the Progression of Esophageal Cancer

Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be capable of playing an important regulatory function in human malignancies. Our study is aimed at delving into the prognostic value and potential function of lncRNA SSTR5-AS1 (SSTR5-AS1) in ESCA. The gene expression data of 182 ESCA samples from TCGA and 653 nontumor specimens from GTEx. The expressions of SSTR5-AS1 were analyzed. We investigated whether there was a correlation between the expression of SSTR5-AS1 and the clinical aspects of ESCA. In order to compare survival curves, the Kaplan-Meier method together with the log-rank test was utilized. The univariate and multivariate Cox regression models were used to analyze the data in order to determine the SSTR5-AS1 expression’s significance as a prognostic factor in ESCA patients. In order to investigate the level of SSTR5-AS1 expression in ESCA cells, RT-PCR was utilized. CCK-8 trials served as a model for the loss-of-function tests. In this study, we found that the expressions of SSTR5-AS1 were increased in ESCA specimens compared with nontumor specimens. According to the ROC assays, high SSTR5-AS1 expression had an AUC value of 0.7812 (95% CI: 0.7406 to 0.8217) for ESCA. Patients who had a high level of SSTR5-AS1 expression had a lower overall survival rate than those who had a low level of SSTR5-AS1 expression. In addition, multivariate analysis suggested that SSTR5-AS1 was an independent predictor of overall survival for ESCA patients. Moreover, RT-PCR experiments indicated that SSTR5-AS1 expression was distinctly increased in three ESCA cells compared with HET1A cells. CCK-8 experiments indicated that silence of SSTR5-AS1 distinctly inhibited the proliferation of ESCA cells. Overall, ESCA patients with elevated SSTR5-AS1 had a worse chance of survival, suggesting it could be used as a prognostic and diagnostic biomarker for ESCA.

Research Article

Ferroptosis-Related Prognostic Gene LAMP2 Is a Potential Biomarker Differential Expressed in Castration Resistant Prostate Cancer

Background. It remains unclear about the mechanisms of prostate cancer progressing to castration resistant prostate cancer (CRPC) and the correlation with ferroptosis. Methods. We compared the gene profiles between localized prostate cancer and metastatic CRPC using the GEO dataset and intersected with a cluster of known ferroptosis-related genes. We received differentially expressed genes (DEGs) in CRPC related to ferroptosis and performed survival analysis to analyze the prognostic values. Furthermore, we conducted single sample gene set enrichment analysis (ssGSEA) to analyze immune infiltration and investigate microRNA crosstalk and methylation for prognostic genes using online databases. Results. We identified 84 DEGs in CRPC related to ferroptosis and 19 hub genes densely connected into networks by enrichment analysis. We performed survival analysis and Cox regression for these genes and identified LAMP2 with significantly prognostic values in overall survival (OS) and disease-specific survival (DSS) of prostate cancer. Furthermore, we found immune infiltration of various immune cells significantly correlated with LAMP2 expression in prostate cancer and identified multiple microRNAs associated with LAMP2 expression in prostate cancer. In addition, we found that the methylation level of LAMP2 in prostate cancer was significantly associated with cancer and identified 8 methylation sites for LAMP2. Conclusion. Ferroptosis-related gene LAMP2 is a potential biomarker with prognostic value for prostate cancer.

Disease Markers
 Journal metrics
See full report
Acceptance rate22%
Submission to final decision61 days
Acceptance to publication23 days
CiteScore4.700
Journal Citation Indicator0.720
Impact Factor3.464
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Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. Read the winning articles.