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Nomograms for Prediction of Molecular Phenotypes in Colorectal Cancer

Authors Yu Z, Yu H, Zou Q, Huang Z, Wang X, Tang G, Bai L, Zhou C, Zhuang Z, Xie Y, Wang H, Xu G, Chen Z, Fu X, Huang M, Luo Y

Received 13 October 2019

Accepted for publication 24 December 2019

Published 13 January 2020 Volume 2020:13 Pages 309—321

DOI https://doi.org/10.2147/OTT.S234495

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche


Zhuojun Yu, 1–3,* Huichuan Yu, 1,* Qi Zou, 1, 4 Zenghong Huang, 1, 2 Xiaolin Wang, 1 Guannan Tang, 1 Liangliang Bai, 1 Chuanhai Zhou, 1–3 Zhuokai Zhuang, 1, 2 Yumo Xie, 1, 2 Heng Wang, 1 Gaopo Xu, 1 Zijian Chen, 1, 5 Xinhui Fu, 1, 6 Meijin Huang, 1, 2 Yanxin Luo 2

1Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 2Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 3Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 4Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 5Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, People’s Republic of China; 6Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Huichuan Yu
Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong 510655, People’s Republic of China
Tel +86-18302044819
Email yuhch5@mail.sysu.edu.cn

Yanxin Luo
Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong 510655, People’s Republic of China
Tel +86-13826190263
Email luoyx25@mail.sysu.edu.cn

Background: Colorectal cancer (CRC) patients with different molecular phenotypes, including microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS gene, vary in treatment response and prognosis. However, molecular phenotyping under adequate quality control in a community-based setting may be difficult. We aimed to build the nomograms based on easily accessible clinicopathological characteristics to predict molecular phenotypes.
Methods: Three hundred and six patients with pathologically confirmed stage I-IV CRC were included in the cohort. The assays for MSI, CIMP, and mutations in BRAF and KRAS gene were performed using resected tumor samples. The candidate predictors were identified from clinicopathological variables using multivariate Logistic regression analyses to construct the nomograms that could predict each molecular phenotype.
Results: The incidences of MSI, CIMP, BRAF mutation and KRAS mutation were 25.3% (72/285), 2.5% (7/270), 3.4% (10/293), and 34.8% (96/276) respectively. In the multivariate Logistic analysis, poor differentiation and high neutrophil/lymphocyte ratio (NLR) were independently associated with MSI; poor differentiation, high NLR and high carcinoembryonic antigen/tumor size ratio (CSR) were independently associated with CIMP; poor differentiation, lymphovascular invasion and high CSR were independently associated with BRAF mutation; poor differentiation, proximal tumor, mucinous tumor and high NLR were independently associated with KRAS mutation. Four nomograms for MSI, CIMP, BRAF mutation and KRAS mutation were developed based on these independent predictors, the C-indexes of which were 61.22% (95% CI: 60.28– 62.16%), 95.57% (95% CI: 95.20– 95.94%), 83.56% (95% CI: 81.54– 85.58%), and 69.12% (95% CI: 68.30– 69.94%) respectively.
Conclusion: We established four nomograms using easily accessible variables that could well predict the presence of MSI, CIMP, BRAF mutation and KRAS mutation in CRC patients.

Keywords: colorectal cancer, microsatellite instability, CpG island methylator phenotype, BRAF, KRAS, nomogram, prediction of molecular subtypes
 

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