Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2019; 11(3): 195-207
Published online Mar 15, 2019. doi: 10.4251/wjgo.v11.i3.195
Human colorectal cancer cells frequently express IgG and display unique Ig repertoire
Zi-Han Geng, Chun-Xiang Ye, Yan Huang, Hong-Peng Jiang, Ying-Jiang Ye, Shan Wang, Yuan Zhou, Zhan-Long Shen, Xiao-Yan Qiu
Zi-Han Geng, Xiao-Yan Qiu, Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Zi-Han Geng, Xiao-Yan Qiu, NHC Key Laboratory of Medical Immunology (Peking University), Beijing 100191, China
Zi-Han Geng, Xiao-Yan Qiu, Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing 100191, China
Chun-Xiang Ye, Hong-Peng Jiang, Ying-Jiang Ye, Shan Wang, Zhan-Long Shen, Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing 100044, China
Chun-Xiang Ye, Hong-Peng Jiang, Ying-Jiang Ye, Shan Wang, Zhan-Long Shen, Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing 100044, China
Yan Huang, Institute of Computational Medicine, School of Artificial Intelligence, Hebei University of Technology, Tianjin 300401, China
Yuan Zhou, Department of Biomedical Informatics, School of Basic Medical Sciences, Center for Noncoding RNA Medicine, Peking University, Beijing 100191, China
Author contributions: Qiu XY and Shen ZL initiated and designed the research; Geng ZH and Ye CX performed all the experiments; Huang Y and Zhou Y carried out data analyzing; Jiang HP contributed in analyzing and interpreting results; Geng ZH and Qiu XY wrote the manuscript; Ye YJ, Wang S contributed in clinical diagnosis of patients; Jiang HP and Shen ZL provided clinical specimens, and clinical and pathological information.
Supported by Key support projects of the National Natural Science Foundation's major research program, No. 91642206; Major international cooperation projects of the National Natural Science Foundation, No. 81320108020; Beijing Natural Science Foundation, No. 7182171; Research institute fund of NHC Key Laboratory of Medical Immunology, Peking University, No. BMU2018JDJS010; and Non-profit central research institute fund of Chinese Academy of Medical Sciences, No. 2018PT31039.
Institutional review board statement: This work is supported by Medical Ethics Committee of Peking University People's Hospital (2018PHB 193-01).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xiao-Yan Qiu, MD, PhD, Doctor, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Xueyuan Road, Beijing 100191, China.
Telephone: +86-10-82805477 Fax: +86-10-82801149
Received: October 26, 2018
Peer-review started: October 26, 2018
First decision: November 14, 2018
Revised: January 3, 2019
Accepted: January 8, 2019
Article in press: January 9, 2019
Published online: March 15, 2019
Research background

Traditionally, immunoglobulin (Ig) was believed to be only produced by B cells; however, studies from our group and others have revealed that except B cells, most of non B cells, especially the non B cancer cells, including the colon cancer cells, can frequently express Ig (non B-Ig). According to our previous findings, cancer cell-derived IgG can significantly promote cancer initiation, progression and metastasis by promoting cancer stem cell behavior. IgG overexpression predicts poor prognosis of patients with cancer. Furthermore, comparing to the B cell-derived Ig repertoire, the non B cancer cell-derived Ig displays restricted and conservative V(D)J pattern rather than diversity. However, we do not know if the colon cancer cell-derived Ig is structurally different from its counterpart normal epithelial cell-derived Ig.

Research motivation

In our previous work, we have found that colon cancer cells can overexpress the IgG compared to normal colonic epithelial cells, but it remains unclear if the colon cancer cell-derived Ig repertoire display unique feature compared to its counterpart normal cell-derived Ig, and whether the unique feature is potential for colon cancer target therapy.

Research objectives

In this study, we used Ig repertoire sequencing (IR-Seq), which allows for the sequencing of millions of V(D)J sequences in parallel, to investigate the Ig repertoire features expressed in human colon cancer cells.

Research methods

We first sorted EPCAM+ colon cancer cells and EPCAM+ normal colonic epithelial cells from corresponding noncancerous tissues as control. Then, using IR-Seq, the expression profile of Ig, VHDJH gene usage of Ig heavy chain (IgH) and somatic hypermutation (SHM) feature in Ig variable region were detected.

Research results

We surprisingly found that comparing to the control normal cells, Ig expressed by colon cancer cells had a significant tendency to choose IgG among the five Ig classes. Furthermore, unlike B-Ig that can generate nearly great diversity, the non B-Ig from either colon cancer or normal epithelial cells showed restricted VHDJH rearrangement patterns. However, comparing to normal cell-derived VHDJH rearrangement patterns, cancer cell-derived VHDJH patterns displayed unique feature, including the usage of VH, D and JH gene, and the SHM feature.

Research conclusions

We found that colon cancer cells could frequently express IgG and unique IgH repertoires, which may be involved in carcinogenesis of colon cancer. The unique IgH repertoire has the potential to be used as a novel target in immune therapy for colon cancer.

Research perspectives

These findings suggest that distinguishing the distinctive mutation sites of cancer cell-derived Ig from normal cell-derived Ig can help finding new target for precise treatment of patients with colon cancer.