AUTHOR=Li Chong , Zhang Keqian , Gong Yuzhu , Wu Qinan , Zhang Yanyan , Dong Yan , Li Dejia , Wang Zhe 

TITLE=Based on cuproptosis-related lncRNAs, a novel prognostic signature for colon adenocarcinoma prognosis, immunotherapy, and chemotherapy response

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1200054

DOI=10.3389/fphar.2023.1200054

ISSN=1663-9812

ABSTRACT=Introduction: Colon adenocarcinoma (COAD) is a special pathological subtype of colorectal cancer (CRC) with highly heterogeneous solid tumor with poor prognosis, and novel biomarkers are urgently needed to guide its prognosis.
Material and methods: RNA-Seq data of COAD were downloaded through The Cancer Genome Atlas (TCGA) database to determine Cuproptosis-related lncRNAs (CRLs) using weighted gene co-expression network analysis (WGCNA). Pathways score was calculated by ssGSEA. CRLs affected prognosis were determined via univariate COX regression analysis to develop a prognostic model using multivariate COX regression analysis and lasso regression analysis. Model was assessed applying Kaplan-Meier (K-M) survival analysis and receiver operating characteristic curves and validated in GSE39582, GSE17538. Tumor microenvironment (TME), single nucleotide variants (SNV), and immunotherapy response/chemotherapy sensitivity were assessed in high- and low-score subgroups. Finally, the construction of nomogram was adopted to predict survival rates of COAD patients during 1, 3 and 5-year(s).
Results: We found that high cuproptosis score reduced survival rates of COAD significantly. A total of 5 CRLs affecting prognosis were identified, containing AC008494.3, EIF3J_DT, AC016027.1, AL731533.2, ZEB1_AS1. The ROC curve showed that RiskScore could perform well in predicting the prognosis of COAD. Meanwhile, we found that RiskScore showed good ability in assessing immunotherapy and chemotherapy sensitivity. Finally, nomogram and decision curves showed that RiskScore would be a powerful predictor for COAD.
Conclusions: A novel prognostic model was constructed using CRLs in COAD, and the CRLs in the model were probably a potential therapeutic target. Based on this study, RiskScore was a new potential and independent predictor factors, immunotherapy response and chemotherapy sensitivity for COAD, providing a new scientific basis for COAD prognosis management.