Survival Prognosis, Tumor Immune Landscape, and Immune Responses of PPP1R18 in Kidney Renal Clear Cell Carcinoma and Its Potentially Double Mechanisms

Abstract

Background:The aim of this study was to investigate the immunological and prognostic roles of protein phosphatase 1 regulatory subunit 18 (PPP1R18) for overall survival (OS) in kidney renal clear cell carcinoma (KIRC) patients, as well as the prediction of its potential mechanisms. Methods:Based on PPP1R18 single gene expression matrices and clinical information from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and GSE6344 datasets, the relationships between PPP1R18 and prognosis/immunity were fully explored. Univariate and multivariate Cox regression analyses were applied to assess its independent prognostic ability and gene set enrichment analysis (GSEA) was implemented to find its related pathways. Besides, we also explored possible mechanisms of PP-P1R18 involved in KIRC.Results: PPP1R18 was highly expressed in KIRC samples than in non-tumor tissues in TCGA, ICGC and GSE6344 datasets, with validations from quantitative real-time polymerase chain reaction (qRT-PCR) in both cell lines and KIRC tissues (all P < 0.05). Univariate and multivariate Cox regression analyses indicated that PPP1R18 was also considered to be with independent prognostic ability in KIRC (both P < 0.01). GSEA results showed that PPP1R18 gene expression was significantly related to Chemokine, JAK STAT, MAPK, and NOTCH pathways. Furthermore, PPP1R18 was also firmly associated with microsatellite instability (MSI), tumor mutational burden (TMB), immune microenvironment, immune cells, immune checkpoints and immune infiltration (all P < 0.05). Analysis of tumor immune dysfunction and exclusion (TIDE) and Imvigor210 datasets suggested that patients with low PPP1R18 expression are more likely to benefit from immunotherapy. Finally, we identified two potential mechanisms of a classical competing endogenous RNA (ceRNA) mechanism and an RNA-binding protein (RBP) involved mechanism of PPP1R18 in KIRC.Conclusions: PPP1R18 played oncogenic and immunological roles of OS in KIRC, offering potential antigens for developing KIRC mRNA vaccines.

SLC9A1 Binding mTOR Signaling Pathway-Derived Risk Score Predicting Survival and Immune in Clear Cell Renal Cell Carcinoma

“…Genetic alterations in MAML3 and the Notch pathway in which it resides also appear to give a better prognosis for patients with ccRCC [36]. As a biomarker for immunotherapy, protein phosphatase 1 regulatory subunit 18 (PPP1R18) serves as an oncogenic role in ccRCC and was signifcantly related with immunity [37]. Te literature confrmed that chromosome condensation 2 (RCC2) was an oncogene and took a crucial part in promoting the proliferation of lung adenocarcinoma, esophageal squamous cell carcinoma, and acute myeloid leukemia [38].…”

PDE1B, a potential biomarker associated with tumor microenvironment and clinical prognostic significance in osteosarcoma

“…To obtain PDE1B related pathways in osteosarcoma, gene set enrichment analysis (GSEA) was applied in high-PDE1B and low-PDE1B subgroups by the GSEA 4.0.0 software with default parameters as previously described 22 , 23 . To reveal the associations between PDE1B gene expression and immunity in osteosarcoma, tumor immune cells infiltration levels and tumor microenvironment were assessed based on the medium expression of the PDE1B gene, classified into high- and low-risk groups.…”

Elevated PTTG1 predicts poor prognosis in kidney renal clear cell carcinoma and correlates with immunity

“…TIDE ( http://tide.dfci.harvard.edu/ ), as a computing architecture, could be used to simulate immune escape from tumors. So, we applied TIDE to predict the immunotherapy responses [ 23 ]. The Cancer Immunome Atlas (TCIA; https://tcia.at/ ) was a dataset of 20 solid cancers with over 8000 tumor samples.…”