Overexpression of GSDMC is a prognostic factor for predicting a poor outcome in lung adenocarcinoma

Abstract

The gasdermin (GSDM) superfamily has been demonstrated to consist of several important molecules that modulate multifunctional signal processes, such as cell pyroptosis. In this research, the roles of the GSDM superfamily on the occurrence and prognosis of lung adenocarcinoma (LUAD) were evaluated using integrative bioinformatic analyses and in vitro methods. Here, data from several bioinformatic platforms revealed that GSDMC is significantly upregulated in LUAD tissues and cell lines. Real-time fluorescence quantitative PCR (qPCR) demonstrated that GSDMC was obviously upregulated in radio-resistant LUAD cells, compared with their parental cells. Moreover, upregulated GSDMC expression was confirmed to be an independent indicator of poor first progression (FP) and overall survival (OS) in LUAD patients. DNA methylation analysis showed an evidently negative correlation between GSDMC expression and methylation status of one CpG site (cg05316065) in its DNA sequence. Patients with high methylation values had significantly higher Karnofsky performance scores (KPSs) and prolonged OS rates. Together, we confirmed that overexpression of GSDMC acts as a promising predictive factor for the poor prognosis of LUAD patients.

Identification of Signatures of Prognosis Prediction for Melanoma Using a Hypoxia Score

“…FERMT1, encoding Kindlin-1, was correlated with metastasis and poor prognosis in several solid tumors ( Liu et al, 2016 ; Sarvi et al, 2018 ). GSDMC functioned as an oncogene, enhancing cell proliferation and tumorigenesis in lung adenocarcinoma and colorectal carcinogenesis ( Miguchi et al, 2016 ; Wei et al, 2020 ). It presented high in malignant melanoma but undetectable in normal epithelial cells, which might be associated with the metastasis of cells ( Xia et al, 2019 ).…”

Channelling inflammation: gasdermins in physiology and disease

“…By contrast, GSDMB expression is suppressed in primary oesophageal and gastric tumours 19 , and its expression correlates with better outcome in patients with bladder carcinoma or melanoma. GSDMC is upregulated in melanoma, colorectal cancer and lung adenocarcinoma, promotes tumour growth and metastasis, and might function as an oncogene in those cancers 82 , 85 , 168 . These studies suggest that the roles of GSDMs in cancer are context, GSDM and cancer type specific, reflecting the complex role of inflammation in tumorigenesis, cancer proliferation and antitumour immunity 169 .…”

8q24.21 Locus: A Paradigm to Link Non-Coding RNAs, Genome Polymorphisms and Cancer

“…Numerous genetic polymorphisms associated with cancer risk are located within the non-coding regions surrounding MYC , which has led to characterising these regions as regulatory elements influencing MYC expression [ 30 ]. Other protein-coding genes within this region have also been shown to contribute to tumourigenesis [ 31 , 32 , 33 , 34 ]. These are FAM84B , GSDMC , FAM49B , and ASAP1 .…”