Transcriptomic correlates of cell cycle checkpoints with distinct prognosis, molecular characteristics, immunological regulation, and therapeutic response in colorectal adenocarcinoma.

Backgrounds

Colorectal adenocarcinoma (COAD), accounting for the most common subtype of colorectal cancer (CRC), is a kind of malignant digestive tumor. Some cell cycle checkpoints (CCCs) have been found to contribute to CRC progression, whereas the functional roles of a lot of CCCs, especially the integrated role of checkpoint mechanism in the cell cycle, remain unclear.

Materials and methods

The Genomic Data Commons (GDC) The Cancer Genome Atlas (TCGA) COAD cohort was retrieved as the training dataset, and GSE24551 and GSE29623 were downloaded from Gene Expression Omnibus (GEO) as the validation datasets. A total of 209 CCC-related genes were derived from the Gene Ontology Consortium and were subsequently enrolled in the univariate, multivariate, and least absolute shrinkage and selection operator (LASSO) Cox regression analyses, finally defining a CCC signature. Cell proliferation and Transwell assay analyses were utilized to evaluate the functional roles of signature-related CCCs. The underlying CCC signature, molecular characteristics, immune-related features, and therapeutic response were finally estimated. The Genomics of Drug Sensitivity in Cancer (GDSC) database was employed for the evaluation of chemotherapeutic responses.

Results

The aberrant gene expression of CCCs greatly contributed to COAD development and progression. Univariate Cox regression analysis identified 27 CCC-related genes significantly affecting the overall survival (OS) of COAD patients; subsequently, LASSO analysis determined a novel CCC signature. Noticeably,

Conclusion

The novel CCC signature exhibited a good ability for prognosis prediction for COAD patients, and the CCC score was found to be highly correlated with molecular features, immune-related characteristics, and therapeutic responses, which would greatly promote clinical management and precision medicine for COAD.

Informations de copyright

Copyright © 2023 Wang, Wang, Wang and Li.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.