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Transcriptome analysis reveals a reprogramming energy metabolism-related signature to improve prognosis in colon cancer.

ABSTRACT: Although much progress has been made to improve treatment, colon cancer remains a leading cause of cancer death worldwide. Metabolic reprogramming is a significant ability of cancer cells to ensure the necessary energy supply in uncontrolled proliferation. Since reprogramming energy metabolism has emerged as a new hallmark of cancer cells, accumulating evidences have suggested that metabolism-related genes may serve as key regulators of tumorigenesis and potential biomarkers. In this study, we analyzed a set of reprogramming energy metabolism-related genes by transcriptome analysis in colon cancer and revealed a five-gene signature that could significantly predict the overall survival. The reprogramming energy metabolism-related signature could distinguish patients into high-risk and low-risk groups with significantly different survival times (P = 0.0011; HR = 1.92; 95% CI [1.29-2.87]). Its prognostic value was confirmed in another two independent colon cancer cohorts (P = 5.2e-04; HR = 2.09, 95%; CI [1.37-3.2] for GSE17538 and P = 3.8e-04; HR = 2.08, 95% CI [1.37-3.16] for GSE41258). By multivariable analysis, we found that the signature was independent of clinicopathological features. Its power in promoting risk stratification of the current clinical stage was then evaluated by stratified analysis. Moreover, the signature could improve the power of the TNM stage for the prediction of overall survival and could be used in patients who received adjuvant chemotherapy. Overall, our results demonstrated the important role of the reprogramming energy metabolism-related signature in promoting stratification of high-risk patients, which could be diagnostic of adjuvant therapy benefit.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7350917 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Transcriptome analysis reveals a reprogramming energy metabolism-related signature to improve prognosis in colon cancer.

Zhang Xinxin X Xu Jinyuan J Lan Yujia Y Guo Fenghua F Xiao Yun Y Li Yixue Y Li Xia X

PeerJ 20200707

Although much progress has been made to improve treatment, colon cancer remains a leading cause of cancer death worldwide. Metabolic reprogramming is a significant ability of cancer cells to ensure the necessary energy supply in uncontrolled proliferation. Since reprogramming energy metabolism has emerged as a new hallmark of cancer cells, accumulating evidences have suggested that metabolism-related genes may serve as key regulators of tumorigenesis and potential biomarkers. In this study, we a ...[more]

PMID: 32704448

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Project description:Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA-cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan-Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5-ACKR1, CCL2-ACKR1, and CCL5-CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

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Transcriptome analysis reveals a reprogramming energy metabolism-related signature to improve prognosis in colon cancer.

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Transcriptome analysis reveals a reprogramming energy metabolism-related signature to improve prognosis in colon cancer.

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