Research Paper Volume 12, Issue 18 pp 18363—18383
A 12-immune cell signature to predict relapse and guide chemotherapy for stage II colorectal cancer
- 1 Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China
- 3 Department of Internal Medicine, People's Hospital of Jinping County, Yunnan Province, China
Received: February 10, 2020 Accepted: July 6, 2020 Published: August 27, 2020
https://doi.org/10.18632/aging.103707How to Cite
Copyright: © 2020 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The management of stage II colorectal cancer is still difficult. We aimed to construct a new immune cell-associated signature for prognostic evaluation and guiding chemotherapy in stage II colorectal cancer. We used the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method to estimate the fraction of 22 immune cells by analyzing bulk tumor transcriptomes and a LASSO Cox regression model to select the prognostic immune cells. A 12-immune cell prognostic classifier, ISCRC, was built, which could successfully discriminate the high-risk patients in the training cohort (GSE39582: HR = 3.16, 95% CI: 1.85–5.40, P < 0.0001) and another independent cohorts (GSE14333: HR = 3.47, 95% CI: 1.18–10.15, P =0.0167). The receiver operating characteristic analysis revealed that the AUC of the ISCRC model was significantly greater than that of oncotypeDX model (0.7111 versus 0.5647, p=0.0152). We introduced the propensity score matching analysis to eliminate the selection bias; survival analysis showed relatively poor prognosis after chemotherapy in stage II CRC patients. Furthermore, a nomogram was built for clinicians and did well in the calibration plots. In conclusion, this immune cell-based signature could improve prognostic prediction and may help guide chemotherapy in stage II colorectal cancer patients.
Abbreviations
AJCC: American Joint Committee on Cancer; AUC: area under receiver operating characteristic; CI: confidence interval; CIBERSORT: Cell Type Identification by Estimating Relative Subsets of RNA Transcripts; CRC: colorectal cancer; DCA: Decision curve analysis; DFS: disease-free survival; GEO: Gene Expression Omnibus; HR: hazard ratio; LASSO: the least absolute shrinkage and selection operator method; MMR: mis-match repair; MSI: microsatellite instability; MSS: microsatellite stable; ROC: receiver operating characteristic.