Research Paper Advance Articles

A 12-immune cell signature to predict relapse and guide chemotherapy for stage II colorectal cancer

Xianglong Tian1, *, , Xiaoqiang Zhu2, *, , Wenying Meng1, *, , Shiguang Bai3, , Min Shi1, , Shihao Xiang1, , Chen Zhao1, , Yugang Wang1, &, ,

  • 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
* Equal contribution

Received: February 10, 2020       Accepted: July 6, 2020       Published: August 27, 2020      

https://doi.org/10.18632/aging.103707
How to Cite

Copyright © 2020 Tian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.