Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer

Abstract

Pancreatic cancer is a digestive system malignant tumor with high mortality and poor prognosis, but the mechanisms of progression remain unclear in pancreatic cancer. It’s necessary to identify the hub genes in pancreatic cancer and explore the novel potential predictors in the prognosis of pancreatic cancer. We downloaded two mRNA expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas Pancreatic Cancer (TCGA-PAAD) datasets to screen the commonly differentially expressed genes in pancreatic cancer by limma package in R. Subsequently, measurement of the functional similarity among the 38 DEGs in common was performed to identify the hub genes using GOSemSim package. Then, survival analysis and Cox regression were applied to explore prognosis-related hub genes using the survival package. Statistics analysis by two-tailed Student’s t-test or one-way based on TCGA-PAAD datasets and qPCR detection in clinical samples were performed to explore the correlations between expression of hub genes in pancreatic cancer tissues and clinical parameters. Based on integrated analysis of TCGA and GEO datasets, we screened 38 DEGs in common, which were all up-regulated. The functional similarity results showed that 10 DEGs including TSPAN1, MSLN, C1orf116, PKP3, CEACAM6, BAIAP2L1, PPL, RAB25, ERBB3, and AP1M2 in the DEGs in common, which had the higher average functional similarity, were considered as the hub genes. Survival analysis results and Cox regression analysis showed that TSPAN1, CEACAM6, as well as ERBB3 were all associated with poor overall survival of PC. qPCR results showed that the expression levels of TSPAN1 and ERBB3 were significantly upregulated in the PC tissues. The statistical analysis results revealed that TSPAN1 expression correlated significantly with histologic grade, T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA; ERBB3 expression correlated significantly with T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA. We found that TSPAN1 and ERBB3 could be independent predictors of poor survival in pancreatic cancer.

Six Genes Associated with Lymphatic Metastasis in Colon Adenocarcinoma Linked to Prognostic Value and Tumor Immune Cell Infiltration

“…The survival package of R software was used for molecular screening of COAD prognosis [ 16 ]. In this part, we used data in the TPM format.…”

“…The R software was used to validate the differential expression of six genes in different groups of COAD patients. The Kaplan–Meier survival curve of six genes was plotted by using a survival package [ 16 ]. Additional prognostic data were derived from an article of Liu's research [ 17 ].…”

“…e Kaplan-Meier survival curve of six genes was plotted by using a survival package [16]. Additional prognostic data were derived from an article of Liu's research [17].…”

Phytochemical‑rich herbal formula ATG‑125 protects against sucrose‑induced gastrocnemius muscle atrophy by rescuing Akt signaling and improving mitochondrial dysfunction in young adult mice

“…Differentially expressed genes (DEGs) with a threshold FDR adjusted, P.adjust <0.05 and fold-change 2 (log2>±1) were selected for further analysis. Principal component analysis (PCA) ( 84 ), volcano plots ggplot2 version 3.3.3 (R package) ( 87 ), Gene Ontology (GO) ( 88 , 89 ), Kyoto Encyclopedia of Genes and Genomes (KEGG) ( 89 ), Disease Ontology (DO) ( 90 ) and Gene Set Enrichment Analysis (GSEA) ( 91 ) enrichment of the DEGs were analyzed. ClusterProfiler package (version 3.14.3) supported the enrichment analysis of GO and KEGG with either hypergeometric tests or GSEA ( 91 ).…”

Assessing the potential relevance of CEACAM6 as a blood transcriptional biomarker

“…Our screening of the CEACAM6 literature, which relates more specifically to its potential relevance as a biomarker in various disease settings, supports this notion. Indeed, a higher abundance of CEACAM6, whether at the transcript or protein level, in tumor tissues or serum was always associated with worse survival (in the case of colorectal, 31,32 breast, 33,34 pancreatic, [35][36][37][38][39] and lung cancers 40 ). Other studies have found CEACAM6 to be of potential value for differential diagnosis of malignant vs benign tumors for breast cancer (with CEACAM6 protein levels measured in breast tissues 41 ) and pancreatic cancer (with CEACAM6 protein levels measured in the bile 42 ).…”