GABRP is a potential prognostic biomarker and correlated with immune infiltration and tumor microenvironment in pancreatic cancer

Abstract

Background: Pancreatic cancer is one of the most commonly diagnosed and lethal malignancies worldwide and has few good biomarkers and therapeutic targets. GABRP is the π subunit of the gamma-aminobutyric acid (GABA) A receptor, which is expressed in a number of non-neuronal tissues. GABRP is significantly upregulated in pancreatic cancer, but its biological and immunological role as well as its clinical diagnostic and prognostic value in pancreatic cancer is still incompletely known.Methods: In this study, pancreatic adenocarcinoma (PAAD) cohorts from TCGA and GEO datasets were used to compare GABRP mRNA levels in cancerous and normal tissues and protein expression was evaluated using immunohistochemistry. The Kaplan-Meier plotter and GEPIA2 database were used to analyze the correlation between GABRP expression, overall survival, and disease-free survival in pancreatic cancer patients. Gene set enrichment analysis (GSEA) was performed with the Linked Omics database to explore the molecular mechanisms of GABRP in pancreatic cancer. And the correlation between GABRP expression and immune infiltration was explored using the TIMER database, CIBERSORT database and ESTIMATE algorithm.Results: GABRP mRNA was significantly overexpressed in TCGA-PAAD cohorts (P<0.0001) and enhanced GABRP expression predicted poorer overall survival according to Kaplan-Meier plotter database (P=0.0024) and GEPIA2 (P=0.038). Hypomethylation of promoter (P<0.01) and the regulation of hsa-miR-3655 may contribute to the overexpression of GABRP in pancreatic cancer. GSEA analysis revealed that GABRP played an important role in the immune response. GABRP expression was also correlated with immune infiltration and immune cell markers. Higher GABRP expression was significantly associated with greater infiltration of immune cells and stromal cells into pancreatic cancer microenvironments as well as higher expression of six important immune check point genes including PDCD1 (P<0.05), CD274 (P<0.05), CTLA4 (P<0.01), PDCD1LG2 (P<0.01), TIGHT (P<0.01) and TIM3 (P<0.01).Conclusions: GABRP is a potential prognostic biomarker and is correlated with immune infiltration and tumor microenvironment in pancreatic cancer. This suggests that GABRP may serve as a potential prognostic biomarker and therapeutic target in pancreatic cancer as well as a possible regulator of tumor microenvironment affecting the efficacy of immunotherapy. Further studies are needed to elucidate the molecular mechanism of the immunoregulatory role of GABRP. We present the following article in accordance with the REMARK reporting checklist (available at https://tcr. amegroups.com/article/view/10.21037/tcr-21-2021/rc). Methods Data collectionThe data on GABRP mRNA expression in pancreatic adenocarcinoma (PAAD) tissues and normal tissues and corresponding clinical data were retrieved from the TCGA

GABRP is a Promising Prognostic Biomarker and Associated with Immune Cell Infiltration in Lung Squamous Cell Carcinoma

“…GABRP was up-regulated in pancreatic cancer, and it was an independent prognostic biomarker for pancreatic cancer patients, this result was consistent with our study. 11 …”

“… 7 GABRP was associated with tumor microenvironment and immune cell infiltration in pancreatic cancer. 11 In addition, the survival advantage of lung cancer patients may be associated with the anti-cancer effect of CD8+/IL-10+ cell phenotype. 20 Previous studies have demonstrated that NK cells could infiltrate lung tumor, implying that the infiltrations of NK cells into cancer cells may benefit the prognosis of patients.…”

“…GABRP was up-regulated in pancreatic 368 cancer, and it was an independent prognostic biomarker for pancreatic cancer patients, this result was consistent with our study. 11 Functional enrichment analysis was performed to further investigate the underlying biological function of GABRPrelated genes in LUSC. GABRP-related genes were mainly involved in various CCs, MFs, KEGGs, such as transporter complex, transmembrane transporter complex, ion channel complex, motile cilium, substrate-specific channel activity, ion channel activity, gated channel activity, taste transduction, nicotine addiction, and starch and sucrose metabolism.…”

“… 10 Furthermore, increased GABRP expression associated with poor prognosis in pancreatic cancer. 11 All these studies revealed that GABRP is closely associated with the tumorigenesis. However, the functional role of GABRP in LUSC and its prognostic value have not been investigated, which deserves further investigation.…”

Identification of hub genes and its relationship with colorectal cancer patient prognosis

“…AURKA mutation had no effect on overall survival time, but impacted the progression free survival time (p = 0.0269). A number of cancer treatments have shown great clinical bene ts from immune checkpoint therapy (ICT) over the past few years [24], solid tumors with macrophage in ltration had poor survival outcomes while those with CD8 + T cells were more likely to survivet [25; 26]. Consequently, we compared immune in ltration landscapes in colorectal cancer and normal populations.…”