Published online Mar 15, 2019. doi: 10.4251/wjgo.v11.i3.195
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
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.
To investigate the Ig repertoire features expressed in human colon cancer cells.
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.
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.
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.
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.