Comprehensive Analysis of Immunoinhibitors Identifies LGALS9 and TGFBR1 as Potential Prognostic Biomarkers for Pancreatic Cancer

Abstract

Pancreatic cancer (PC) is one of the most deadly cancers worldwide. To uncover the unknown novel biomarker used to indicate early diagnosis and prognosis in the molecular therapeutic field of PC is extremely of importance. Accumulative evidences indicated that aberrant expression or activation of immunoinhibitors is a common phenomenon in malignances, and significant associations have been noted between immunoinhibitors and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of immunoinhibitors contributing to tumorigenesis and progression of pancreatic cancer (PC) have not yet been elucidated clearly. In this study, we investigated the distinct expression and prognostic value of immunoinhibitors in patients with PC by analyzing a series of databases, including TISIDB, GEPIA, cBioPortal, and Kaplan-Meier plotter database. The mRNA expression levels of IDO1, CSF1R, VTCN1, KDR, LGALS9, TGFBR1, TGFB1, IL10RB, and PVRL2 were found to be significantly upregulated in patients with PC. Aberrant expression of TGFBR1, VTCN1, and LGALS9 was found to be associated with the worse outcomes of patients with PC. Bioinformatics analysis demonstrated that LGALS9 was involved in regulating the type I interferon signaling pathway, interferon-gamma-mediated signaling pathway, RIG-I-like receptor signaling pathway, NF-kappa B signaling pathway, cytosolic DNA-sensing pathway, and TNF signaling pathway. And TGFB1 was related to mesoderm formation, cell matrix adhesion, TGF-beta signaling pathway, and Hippo signaling pathway. These results suggested that LGALS9 and TGFBR1 might serve as potential prognostic biomarkers and targets for PC.

CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

“…TGFB1, mainly secreted by TAMs and CAFs in TME, play an irreplaceable role in inducing immunosuppressive microenvironment. Immunosuppressive genes, such as IL10, IL10RB, LGALS9, and LAG3, were observed to be co-overexpressed with TGFB1 in tumor tissues and predicted poor survival of tumor patients, indicating a potential mechanism by which CCDC137 regulates macrophage polarization, CAFs formation and correlates with several immunosuppressive genes ( Kadowaki et al, 2016 ; Fan et al, 2020 ; Suzuki et al, 2021 ; Wang et al, 2021 ). In addition, the high expression of CCDC137 indicates the immunosuppression status in LGG and UVM, providing a potential drug target for tumor therapy.…”

Comprehensive Analysis of the Prognostic Value and Immune Function of Immune Checkpoints in Stomach Adenocarcinoma

“… 24 Another study suggested LGALS9 and TGFBR1 as novel biomarkers for the prognosis of pancreatic cancer. 25 Li et al found that ICOSLG act as prognostic biomarker in esophageal squamous cell carcinoma associated with an unfavorable overall survival. 26 In colorectal cancer, CD274 was suggested as prognosis biomarker and it could predict the response to anti-PD-1 therapy.…”

PD-L1 activity is associated with partial EMT and metabolic reprogramming in carcinomas

“…Multiple inflammatory pathways such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and nuclear factor-kappa B (NF-κB) are known to induce PD-L1 [50]. Another immune checkpoint marker, LGALS9, was reported to be involved in regulating many of these inflammatory pathways [51]. Thus, we conducted a correlation analysis to elucidate the connection between CD274 (PD-L1 gene) and immune checkpoint markers used earlier (CD47, CD276, CTLA4, HAVCR2, LAG3, LGALS9 and PDCD1).…”