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Mol Oncol. 2014 Dec;8(8):1653-66. doi: 10.1016/j.molonc.2014.06.016. Epub 2014 Jul 4.

A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients.

Author information

1
Medical Genomics Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
2
Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea; Department of Cancer Research, Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Centre, Seoul, Korea.
3
Department of Cancer Research, Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Centre, Seoul, Korea; Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Korea.
4
Medical Genomics Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; Department of Cancer Research, Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Centre, Seoul, Korea. Electronic address: yongsung@kribb.re.kr.
5
Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea; Department of Cancer Research, Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Centre, Seoul, Korea. Electronic address: jckim@amc.seoul.kr.

Abstract

Colorectal cancer (CRC) patients frequently experience disease recurrence and distant metastasis. This study aimed to identify prognostic indicators, including individual responses to chemotherapy, in CRC patients. RNA-seq data was generated using 54 samples (normal colon, primary CRC, and liver metastases) from 18 CRC patients and genes associated with CRC aggressiveness were identified. A risk score based on these genes was developed and validated in four independent CRC patient cohorts (n = 1063). Diverse statistical methods were applied to validate the risk scoring system, including a generalized linear model likelihood ratio test, Kaplan-Meier curves, a log-rank test, and the Cox model. TREM1 and CTGF were identified as two activated regulators associated with CRC aggressiveness. A risk score based on 19 genes regulated by TREM1 or CTGF activation (TCA19) was a significant prognostic indicator. In multivariate and subset analyses based on pathological staging, TCA19 was an independent risk factor (HR = 1.894, 95% CI = 1.227-2.809, P = 0.002). Subset stratification in stage III patients revealed that TCA19 had prognostic potential and identified patients who would benefit from adjuvant chemotherapy, regardless of age. The TCA19 predictor represents a novel diagnostic tool for identifying high-risk CRC patients and possibly predicting the response to adjuvant chemotherapy.

KEYWORDS:

Chemotherapy; Colorectal cancer; Markers; Metastasis; Prognosis

PMID:
25049118
PMCID:
PMC5528589
DOI:
10.1016/j.molonc.2014.06.016
[Indexed for MEDLINE]
Free PMC Article

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