Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues based on four Gene Expression Omnibus (GEO) datasets (GSE15471, GSE16515, GSE28735 and GSE71729). A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE and Human Protein Atlas (HPA) databases, as well as the validation GEO dataset GSE62452. Additionally, the prognostic values of the hub genes were evaluated by Kaplan–Meier plotter and the validation GEO dataset GSE62452. Finally, the mechanistic roles of the most remarkable hub genes in PDAC were examined through in vitro experiments. Results: We identified the following nine hub genes by performing an integrated bioinformatics analysis: COL1A1, COL1A2, FN1, ITGA2, KRT19, LCN2, MMP9, MUC1 and VCAN. All of the hub genes were significantly upregulated in PDAC tissues compared with normal pancreatic tissues. Two hub genes (FN1 and ITGA2) were associated with poor overall survival (OS) rates in PDAC patients. Finally, in vitro experiments indicated that FN1 plays vital roles in PDAC cell proliferation, colony formation, apoptosis and the cell cycle. Conclusions: In summary, we identified two hub genes that are associated with the expression and prognosis of PDAC. The oncogenic role of FN1 in PDAC was first illustrated by performing an integrated bioinformatic analysis and in vitro experiments. Our results provide a fundamental contribution for further research aimed finding novel therapeutic targets for overcoming PDAC.

Yizhi Li, Ge Zhang, Bohao Yang, Chenghua Lin, Anton Ragni, Shi Wang, Jie Fu. Findings of the Association for Computational Linguistics: AACL-IJCNLP 2022. 2022.

Background: Ovarian cancer (OC) is one of the most life-threatening cancers affecting women worldwide. Recent studies have shown that the DNA methylation state can be used in the diagnosis, treatment and prognosis prediction of diseases. Meanwhile, it has been reported that the DNA methylation state can affect the function of immune cells. However, whether DNA methylation-related genes can be used for prognosis and immune response prediction in OC remains unclear. Methods: In this study, DNA methylation-related genes in OC were identified by an integrated analysis of DNA methylation and transcriptome data. Prognostic values of the DNA methylation-related genes were investigated through least absolute shrinkage and selection operator (LASSO) and Cox progression analyses. Immune characteristics were investigated by CIBERSORT, correlation analysis and weighted gene co-expression network analysis (WGCNA). Results: Twelve prognostic genes (CA2, CD3G, HABP2, KCTD14, PI3, SERPINB5, SLAMF7, SLC9A2, STC2, TBP, TREML2 and TRIM27) were identified and a risk score signature and a nomogram based on prognostic genes and clinicopathological features were constructed for the survival prediction of OC patients in the training and two validation cohorts. Subsequently, the differences in the immune landscape between the high- and low-risk score groups were systematically investigated. Conclusions: Taken together, our study explored a novel efficient risk score signature and a nomogram for the survival prediction of OC patients. In addition, the differences of the immune characteristics between the two risk groups were clarified preliminarily, which will guide the further exploration of synergistic targets to improve the efficacy of immunotherapy in OC patients.

Background: Abnormal DNA methylation is one of the most general epigenetic modifications in hepatocellular carcinoma (HCC). Recent research showed that DNA methylation was a prognostic indicator of all‐cause HCC and nonviral HCC. However, whether DNA methylation‐driver genes could be used for predicting survival, the probability of hepatitis‐positive HCC remains unclear.Methods: In this study, DNA methylation‐driver genes (MDGs) were screened by a joint analysis of methylome and transcriptome data of 142 hepatitis‐positive HCC patients. Subsequently, a prognostic risk score and nomogram were constructed. Finally, correlation analyses between the risk score and signaling pathways and immunity were conducted by GSVA and CIBERSORT.Results: Through random forest screening and Cox progression analysis, 10 prognostic methylation‐driver genes (AC008271.1, C11orf53, CASP8, F2RL2, GBP5, LUCAT1, RP11‐114B7.6, RP11‐149I23.3, RP11‐383 J24.1, and SLC35G2) were screened out. As a result, a prognostic risk score signature was constructed. The independent value of the risk score for prognosis prediction were addressed in the TCGA‐HCC and the China‐HCC cohorts. Next, clinicopathological features were analyzed and HBV status and histological grade were screened to construct a nomogram together with the risk score. The prognostic efficiency of the nomogram was validated by the calibration curves and the concordance index (C index: 0.829, 95% confidence interval: 0.794–0.864), while its clinical application ability was confirmed by decision curve analysis (DCA). At last, the relationship between the risk score and signaling pathways, as well as the correlations between immune cells were elucidated preliminary.Conclusions: Taken together, our study explored a novel DNA methylation‐driver gene risk score signature and an efficient nomogram for long‐term survival prediction of hepatitis‐positive HCC patients.