A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility

Abstract

Disulfidptosis, a novel type of programmed cell death, has attracted researchers’ attention worldwide. However, the role of disulfidptosis-related lncRNAs (DRLs) in liver hepatocellular carcinoma (LIHC) not yet been studied. We aimed to establish and validate a prognostic signature of DRLs and analyze tumor microenvironment (TME) and drug susceptibility in LIHC patients. RNA sequencing data, mutation data, and clinical data were obtained from the Cancer Genome Atlas Database (TCGA). Lasso algorithm and cox regression analysis were performed to identify a prognostic DRLs signature. Kaplan–Meier curves, principal component analysis (PCA), nomogram and calibration curve, function enrichment, TME, immune dysfunction and exclusion (TIDE), tumor mutation burden (TMB), and drug sensitivity analyses were analyzed. External datasets were used to validate the predictive value of DRLs. qRT-PCR was also used to validate the differential expression of the target lncRNAs in tissue samples and cell lines. We established a prognostic signature for the DRLs (MKLN1-AS and TMCC1-AS1) in LIHC. The signature could divide the LIHC patients into low- and high-risk groups, with the high-risk subgroup associated with a worse prognosis. We observed discrepancies in tumor-infiltrating immune cells, immune function, function enrichment, and TIDE between two risk groups. LIHC patients in the high-risk group were more sensitive to several chemotherapeutic drugs. External datasets, clinical tissue, and cell lines confirmed the expression of MKLN1-AS and TMCC1-AS1 were upregulated in LIHC and associated with a worse prognosis. The novel signature based on the two DRLs provide new insight into LIHC prognostic prediction, TME, and potential therapeutic strategies.

Development and validation of a novel disulfidptosis-related lncRNAs signature in patients with HPV-negative oral squamous cell carcinoma

“…LncRNAs undertake a critical part in modulating malignant behaviors of tumors and have been deemed as possible tumortargets in recent years 43 . DRLs signatures have been reported to forecast survival in various cancers, including www.nature.com/scientificreports/ colon adenocarcinoma 44 , hepatocellular carcinoma 45 , and glioma 46 . Hitherto, there are limited studies on survival significance between DRLs and HPV-negative OSCC.…”