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: http://creativecommons.org/licenses/by-nc/4.0/
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. qiuxy@bjmu.edu.cn
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
Processing time: 140 Days and 19.2 Hours
Abstract
BACKGROUND

There is growing evidence proving that many human carcinomas, including colon cancer, can overexpress immunoglobulin (Ig); the non B cancer cell-derived Ig usually displayed unique V(D)J rearrangement pattern that are distinct from B cell-derived Ig. Especially, the cancer-derived Ig plays important roles in cancer initiation, progression, and metastasis. However, it still remains unclear if the colon cancer-derived Ig can display unique V(D)J pattern and sequencing, which can be used as novel target for colon cancer therapy.

AIM

To investigate the Ig repertoire features expressed in human colon cancer cells.

METHODS

Seven cancerous tissue samples of colon adenocarcinoma and corresponding noncancerous tissue samples were sorted by fluorescence-activated cell sorting using epithelial cell adhesion molecule as a marker for epithelial cells. Ig repertoire sequencing was used to analyze the expression profiles of all 5 classes of Ig heavy chains (IgH) and the Ig repertoire in colon cancer cells and corresponding normal epithelial cells.

RESULTS

We found that all 5 IgH classes can be expressed in both colon cancer cells and normal epithelial cells. Surprisingly, unlike the normal colonic epithelial cells that expressed 5 Ig classes, our results suggested that cancer cells most prominently express IgG. Next, we found that the usage of Ig in cancer cells caused the expression of some unique Ig repertoires compared to normal cells. Some VH segments, such as VH3-7, have been used in cancer cells, and VH3-74 was frequently present in normal epithelial cells. Moreover, compared to the normal cell-derived Ig, most cancer cell-derived Ig showed unique VHDJH patterns. Importantly, even if the same VHDJH pattern was seen in cancer cells and normal cells, cancer cell-derived IgH always displayed distinct hypermutation hot points.

CONCLUSION

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.

Keywords: Immunoglobulin repertoire; Sequencing; Colorectal cancer; VDJ pattern; VJ pattern

Core tip: It has been found that colon cancer cells can express immunoglobulin (Ig); however, the expression profile and features of the Ig repertoire in colon cancer cells remain unclear. Here, we first sorted colon cancer cells and normal cells from 7 patients with colon cancer. Using the Ig repertoire sequencing, we analyzed the features of the Ig heavy chain (IgH) repertoire in these cells. We found that Ig in colon cancer cells had a significant tendency to choose IgG compared to the other classes of IgH, and showed unique VHDJH patterns and somatic hypermutation hotspots, which might be potential targets for immune therapy for colon cancer.