Identification of Immune-Related lncRNA Pairs and Construction and Validation of a New Prognostic Signature of Colon Cancer.

Abstract

Background:

More and more evidence has shown that immune-related long noncoding ribonucleic acid (irlncRNAs) is a potential prognostic factor for colon cancer. The relevant gene pair pattern can improve the sensitivity of the prognostic model. Therefore, our present study aimed to identify irlncRNA Pairs and construct and validate a new prognostic signature in colon cancer.

Methods:

We downloaded the expression matrix of mRNA and lncRNA of patients with colon cancer and their clinical information from the public TCGA database. We obtained immune genes from the ImmPort database. Coexpression analysis was performed to identify irlncRNAs. We built an irlncRNA pair matrix by comparing the expression levels of each lncRNA pair in a cycle. Univariate Cox regression analysis, LASSO penalized regression analysis, and multivariate Cox regression analysis were performed to determine the final variables to construct the prognostic risk score model (a new signature). We draw the receiver operating characteristic (ROC) curves of the signature and clinical characteristics and determine the optimal cutoff value by the optimal Akaike Information Criterion (AIC) value. Based on the optimal cutoff value of the ROC curve of the signature, colon cancer patients were divided into the high- and low-risk groups. Then, the signature was evaluated by clinicopathological features, tumor-infiltrating immune cells, checkpoint-related biomarkers, targeted therapy, and chemotherapy.

Results:

We identified 8 lncRNA pairs including AC103740.1|LEF1-AS1, LINC02391|AC053503.5, WWC2-AS2|AL355916.2, AC104090.1|NEURL1-AS1, AC099524.1|AL161908.1, AC074011.1|AL078601.2, AL355916.2|LINC01723, and AP003392.4|LINC00598 from 71 differently expressed irlncRNAs. We constructed a prognostic risk score model (a new signature) using these optimal eight irlncRNA pairs. ROC curve analysis revealed that the highest AUC value of the signature was 0.776 at 1 year, with the optimal cutoff value of 1.283. Our present study also showed that the constructed signature could accurately identify adverse survival outcomes, prognostic clinicopathological features, and specify tumor invasion status. The expression of immune checkpoint-related genes and chemical drug sensitivity were related to different risk groups.

Conclusion:

In our present study, we constructed a new irlncRNA signature of colon cancer based on the irlncRNA pairs instead of the special expression level of lncRNA. We found this signature had not only good prognostic value but also certain clinical value, which might provide a new insight into the treatment and prognosis of colon cancer.

• Authors: Minxian Xu, Qing Li, Jianfang Zhang, Hui Xie
• Journal: Canadian journal of gastroenterology & hepatology (Can J Gastroenterol Hepatol) Vol. 2022 Pg. 5827544 ( 2022) ISSN: 2291-2797 [Electronic] Egypt
• PMID: 35399646 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Minxian Xu et al.

Chemical References

• Biomarkers, Tumor
• RNA, Long Noncoding

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Colonic Neoplasms (genetics, pathology)
• Humans
• Prognosis
• RNA, Long Noncoding (genetics)
• ROC Curve