High HBV Load Weakens Predictive Effect of Serum miR-122 on Response to Sorafenib in Hepatocellular Carcinoma PatientsRead the full article
Journal of Oncology publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.
Journal of Oncology maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.
Latest ArticlesMore articles
Exploration of the Key Proteins in the Normal-Adenoma-Carcinoma Sequence of Colorectal Cancer Evolution Using In-Depth Quantitative Proteomics
Purpose. In most cases, the carcinogenesis of colorectal cancer (CRC) follows the normal-adenoma-carcinoma (N-A-C) sequence. In this study, we aimed to identify the key proteins in the N-A-C sequence. Methods. Differentially expressed proteins (DEPs) in normal, adenoma, and carcinoma tissues were identified using the Tandem Mass Tag- (TMT-) based quantitative proteomics approach. The landscape of proteomic variation in the N-A-C sequence was explored using gene set enrichment analysis (GSEA) and Proteomaps. Key proteins in the N-A-C sequence were identified, verified, and validated based on our proteomic data, external proteomic data, and external transcriptomic data in the ProteomeXchange, CPTAC, GEO, and TCGA databases. The prognostic value of the key proteins in our database was evaluated by univariate and multivariate Cox regression analysis. The effects of the key proteins on adenoma organoids and colorectal cancer cells were explored in functional studies. Results. Based on our proteomic profiles, we identified 1,294 DEPs between the carcinoma (CG) and normal (NG) groups, 919 DEPs between the adenoma group (AG) and NG, and 1,030 DEPs between the CG and AG. Ribosome- and spliceosome-related pathways were mainly enriched in the N-A process. Extracellular matrix- and epithelial-mesenchymal transition- (EMT-) related pathways were mainly enriched in the A-C process. RRP12 and SERPINH1 were identified, verified, and validated as candidate key proteins in the N-A and A-C processes, respectively. Furthermore, RRP12 and SERPINH1 knockdown impeded the viability and proliferation of adenoma organoids. SERPINH1 was validated as a risk factor for disease-free survival (DFS) based on the TCGA and our database, whereas RRP12 did not show prognostic value. SERPINH1 knockdown was accompanied by EMT-related protein variation, increased apoptosis, and reduced proliferation, invasion, and migration of CRC cells in vitro. Conclusions. RRP12 and SERPINH1 may play an important role in the N-A and A-C processes, respectively. Furthermore, SERPINH1 showed favorable prognostic value for DFS in CRC patients. We speculate that SERPINH1 might promote not only the A-C process but also the development of CRC.
Chidamide and Radiotherapy Synergistically Induce Cell Apoptosis and Suppress Tumor Growth and Cancer Stemness by Regulating the MiR-375-EIF4G3 Axis in Lung Squamous Cell Carcinomas
As a selective histone deacetylase (HDAC) inhibitor developed in China, chidamide has been applied for the treatment of refractory peripheral T-cell lymphoma (PTCL) and multiple solid tumors, including lung cancer. However, the underlying mechanisms are not well elucidated. In our present study, we found that chidamide and radiation acted synergistically to suppress cell and xenograft growth of lung squamous cell carcinoma cells by inducing cell apoptosis. Moreover, chidamide alone or a combination of chidamide and radiation treatment inhibited cancer cell stemness. miRNA microarray analysis demonstrated that miR-375 was the highest upregulated microRNA (miRNA) in NCI-2170 and NCI-H226 cells treated with chidamide alone or treated with chidamide plus radiation, compared with normal control. Inhibition of miR-375 attenuated the promoting effect of chidamide alone and chidamide plus radiation-induced NCI-2170 and NCI-H226 cell apoptosis and reverted the suppression of cancer stemness caused by chidamide alone or chidamide plus radiation treatment. Moreover, EIF4G3, a scaffold protein in the translation initiation complex, was found to be a direct target of miR-375 based on the luciferase reporter assay and western blot analysis. Interestingly, both chidamide alone and chidamide plus radiation treatments suppressed the mRNA and protein expression of EIF4G3. Silence of EIF4G3 also induced cell apoptosis and suppressed tumor growth in NCI-2170 and NCI-H226 cells. These data suggest that chidamide shows a synergistic effect with radiation therapy on lung squamous cell carcinomas by modulating the miR-375-EIF4G3 axis, which may afford an effective strategy to overcome the drug resistance of chidamide in clinical cancer therapy.
Investigation of Radiation-Induced Toxicity in Head and Neck Cancer Patients through Radiomics and Machine Learning: A Systematic Review
Background. Radiation-induced toxicity represents a crucial concern in oncological treatments of patients affected by head and neck neoplasms, due to its impact on survivors’ quality of life. Published reports suggested the potential of radiomics combined with machine learning methods in the prediction and assessment of radiation-induced toxicities, supporting a tailored radiation treatment management. In this paper, we present an update of the current knowledge concerning these modern approaches. Materials and Methods. A systematic review according to PICO-PRISMA methodology was conducted in MEDLINE/PubMed and EMBASE databases until June 2019. Studies assessing the use of radiomics combined with machine learning in predicting radiation-induced toxicity in head and neck cancer patients were specifically included. Four authors (two independently and two in concordance) assessed the methodological quality of the included studies using the Radiomic Quality Score (RQS). The overall score for each analyzed study was obtained by the sum of the single RQS items; the average and standard deviation values of the authors’ RQS were calculated and reported. Results. Eight included papers, presenting data on parotid glands, cochlea, masticatory muscles, and white brain matter, were specifically analyzed in this review. Only one study had an average RQS was ≤ 30% (50%), while 3 studies obtained a RQS almost ≤ 25%. Potential variability in the interpretations of specific RQS items could have influenced the inter-rater agreement in specific cases. Conclusions. Published radiomic studies provide encouraging but still limited and preliminary data that require further validation to improve the decision-making processes in preventing and managing radiation-induced toxicities.
Protective Effect of Quercetin Nanoemulsion on 5-Fluorouracil-Induced Oral Mucositis in Mice
The target of this study was to evaluate the efficacy, histopathological, oxidative stress, and molecular effects of quercetin (QRC) in mice with oral mucositis induced by 5-fluorouracil (5-FU). Thirty-six albino male mice with oral mucositis induced by 5-FU as a chemotherapeutic agent were used in this study. The animals were randomly divided into 6 groups: control group, mucositis (MUC) group, pretreatment group, posttreatment group, and two last groups including nanoemulsion form of QRC with a dose of 5 mg/kg in both pretreatment and posttreatment. In the present evaluation, fewer oral lesions were observed in the QRC posttreatment groups compared to the pretreatment and nanoemulsion receiving groups. In the SOD assay, the most significant difference was observed in the posttreatment nanogroup (41.073 ± 1.24) and pretreatment nanogroup (43.453 ± 2.60) in comparison to the 5-FU group (30.897 ± 1.93). The results of CAT assay also showed a significant difference in nano-posttreatment (124.60 ± 10.85), posttreatment (135.4 ± 9.82), and nano-pretreatment groups (128.80 ± 7.20) compared to the 5-FU group (55.07 ± 8.91). The expression of inflammatory genes such as Hif-1α and NfκB in this group was lower than in the other groups, although this difference was not significant. It seems that the use of QRC can improve the treatment process of oral mucositis induced by 5-FU.
Comprehensive Analysis of Differentially Expressed Long Noncoding RNA-mRNA in the Adenoma-Carcinoma Sequence of DNA Mismatch Repair Proficient Colon Cancer
DNA proficient mismatch repair colon cancer (pMMR CC) is the most common subtype of sporadic CC. We aimed to investigate the role of long noncoding RNAs (lncRNAs) in pMMR CC carcinogenesis. In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and coexpression network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values compared to serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. In conclusion, several lncRNAs play various roles in the adenoma-carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.
Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis
Background. Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC. Materials and Methods. RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion. Results. Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression. Conclusions. WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.