Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

Zhonglin Zhu; Qiuyan Zhao; Shanbao Li; Junyong Weng; Tianan Guo; Congcong Zhu; Ye Xu

doi:10.3389/fgene.2022.984743

Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

Front Genet. 2022 Nov 17:13:984743. doi: 10.3389/fgene.2022.984743. eCollection 2022.

Authors

Zhonglin Zhu^{1

2}, Qiuyan Zhao^{3

4}, Shanbao Li⁵, Junyong Weng^{1

2}, Tianan Guo^{1

2}, Congcong Zhu^{1

2}, Ye Xu^{1

2}

Affiliations

¹ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: Cuproptosis is a novel form of cell death discovered in recent. A great quantity of researches has confirmed the close relationships and crucial roles between long non-coding RNAs (lncRNAs) with the progression of colorectal cancer (CRC). However, the relationship between cuproptosis and lncRNAs remains unclear in CRC. Methods: 1,111 co-expressed lncRNAs with 16 cuproptosis regulators were retrieved from CRC samples of The Cancer Genome Atlas (TCGA) database. Through univariate Cox and least absolute shrinkage and selection operator regression analysis, a prognosis model was constructed with 15 lncRNAs. The Kaplan-Meier, receiver operating characteristic curve, C-index and principal component analysis identified the prognostic power. Furthermore, a cuproptosis-related cluster was generated based on the 15 lncRNAs by unsupervised methods. The correlations between the cuproptosis-related signatures with immune cell infiltration and anti-tumor therapy were explored by multiple algorithms. Results: A risk score and nomogram with great prediction ability were constructed for CRC prognosis evaluation. The immune activate pathways, immune infiltration cells, immune functions, immune score and immune activation genes were remarkably enriched in the high risk group. The cuproptosis-related cluster was generated, of which the cluster 2 showed longer overall survival. The immune cell infiltration analysis indicated the similar results of cluster 2 with the high risk group, implying a significant marker for "hot tumor." The cluster 2 also presented high expression of immune checkpoint molecules, MSI-H status and higher susceptibility to multiple immunotherapy drugs. Conclusion: We appraised a novel cuproptosis-related prognosis model and molecular signature associated with prognosis, immune infiltration and immunotherapy. The identification of cuproptosis-related lncRNAs improved our understanding of immune infiltration and provided a significant marker for prognosis and immunotherapy in CRC.

Keywords: colorectal cancer; cuproptosis; immune infiltration; long non-coding RNA; prognosis.