Relationship between a 7-mRNA signature of the pancreatic adenocarcinoma microenvironment and patient prognosis (a STROBE-compliant article)

Abstract

The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes. The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database. A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group ( P < .0001, P = .0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part. A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.

Identification of Prognostic Genes in the Tumor Microenvironment of Hepatocellular Carcinoma

“…It has prognostic significance in Dukes'B colon cancer ( 52 ) and glioblastoma ( 53 ). Besides, the GBP5 gene has been studied in a variety of cancers, including gastric adenocarcinoma ( 54 ), skin cutaneous melanoma ( 55 , 56 ), pancreatic adenocarcinoma ( 57 ), and HCC, and GBP5 was one of the key genes in the malignant transformation induced by microcystin-LR (MC-LR) in the cell of HCC ( 58 ). In addition, GBP5 promotes immunity in mammals.…”

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

“…The Over Representation Analysis indicates that the package identified module M6 (Figure 5E). The top 13 genes were linked with two primary mechanisms, inflammation and immune regulation and DNA repair and genome stability mechanisms. Inflammation and immune regulation: Genes including HMGB3, IGBP1, LIF, P2RY6 and ESR1 are implicated in inflammatory responses and immune regulation 60–63 . These are potentially associated with inflammatory skin conditions such as eczema and psoriasis. DNA repair and genome stability: Genes such as BRCA1, DHX15, PRKDC and CBL participate in DNA repair and the maintenance of genome stability.…”

Vertebrate Cell Differentiation, Evolution, and Diseases: The Vertebrate-Specific Developmental Potential Guardians VENTX/NANOG and POU5/OCT4 Enter the Stage

“…Several mutation-driver genes (Mut-driver-genes) have been characterized in cancer cells so far (e.g., KRAS , BRAF , MYC , TP53 ), however vsDPGs have gained attention in the process of carcinogenesis due to their tumorigenic potential [ 145 , 146 , 147 ]. VENTX and NANOG were found highly expressed in brain (glioma/glioblastoma) [ 148 , 149 , 150 ], pancreatic [ 151 , 152 , 153 ] renal [ 154 , 155 ], esophageal [ 156 , 157 ] and testicular cancers [ 28 , 158 , 159 ]. Interestingly, VENTX and NANOG share activity in hematopoiesis by repressing the genes responsible for terminal differentiation (e.g., TAL1 , KLF1 ) [ 160 , 161 ], as well as promoting leukemia [ 161 , 162 , 163 ].…”