Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms

Abstract

Background: Colon cancer, a prevalent and deadly malignancy worldwide, ranks as the third leading cause of cancer-related mortality. Disulfidptosis stress triggers a unique form of programmed cell death known as disulfidoptosis, characterized by excessive intracellular cystine accumulation. This study aimed to establish reliable bioindicators based on long non-coding RNAs (LncRNAs) associated with disulfidptosis-induced cell death, providing novel insights into immunotherapeutic response and prognostic assessment in patients with colon adenocarcinoma (COAD).Methods: Univariate Cox proportional hazard analysis and Lasso regression analysis were performed to identify differentially expressed genes strongly associated with prognosis. Subsequently, a multifactorial model for prognostic risk assessment was developed using multiple Cox proportional hazard regression. Furthermore, we conducted comprehensive evaluations of the characteristics of disulfidptosis response-related LncRNAs, considering clinicopathological features, tumor microenvironment, and chemotherapy sensitivity. The expression levels of prognosis-related genes in COAD patients were validated using quantitative real-time fluorescence PCR (qRT-PCR). Additionally, the role of ZEB1-SA1 in colon cancer was investigated through CCK8 assays, wound healing experiment and transwell experiments.Results: disulfidptosis response-related LncRNAs were identified as robust predictors of COAD prognosis. Multifactorial analysis revealed that the risk score derived from these LncRNAs served as an independent prognostic factor for COAD. Patients in the low-risk group exhibited superior overall survival (OS) compared to those in the high-risk group. Accordingly, our developed Nomogram prediction model, integrating clinical characteristics and risk scores, demonstrated excellent prognostic efficacy. In vitro experiments demonstrated that ZEB1-SA1 promoted the proliferation and migration of COAD cells.Conclusion: Leveraging medical big data and artificial intelligence, we constructed a prediction model for disulfidptosis response-related LncRNAs based on the TCGA-COAD cohort, enabling accurate prognostic prediction in colon cancer patients. The implementation of this model in clinical practice can facilitate precise classification of COAD patients, identification of specific subgroups more likely to respond favorably to immunotherapy and chemotherapy, and inform the development of personalized treatment strategies for COAD patients based on scientific evidence.

ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma

“…Although a number of disulfidptosis-related lncRNA prognostic signatures can predict the survival of cancer patients [ 35 , 36 , 37 ], the involvement of individual lncRNAs in disulfidptosis remains to be experimentally validated. This study is the first to identify an individual lncRNA that can be regarded as a regulatory factor in disulfidptosis.…”

Exploiting cell death and tumor immunity in cancer therapy: challenges and future directions

“…Through the discussion of various therapeutic approaches inducing programmed cell death and immune cell death, we have discovered that many treatments have strong limitations, benefiting only certain tumor types with specific characteristics, such as patients with myeloproliferative neoplasms carrying CALR mutations showing better outcomes ( Fucikova et al, 2021 ; Huang X. et al, 2023 ; Chi et al, 2023 ; Zhao et al, 2023 ). Therefore, it is crucial to effectively utilize current hot topics like single-cell analysis and other diagnostic tools to classify patients who can or cannot benefit from treatment earlier, faster, and more accurately through cell markers.…”

Integrating disulfidptosis-related long noncoding RNAs in colorectal cancer prognosis: A path to precision medicine

“…This advancement could revolutionize precision medicine by enabling more personalized and effective treatments. Future research is essential to understand DRLs' impact on CRC progression and treatment response, and their viability as therapeutic targets, potentially leading to innovative treatments that significantly improve patient outcomes[ 5 ]. Validating the functions of disulfidptosis-related lncRNAs and immune checkpoints' anti-cancer mechanisms through comprehensive animal and cell studies is imperative.…”