Cancer IgG, a potential prognostic marker, promotes colorectal cancer progression.

Hongpeng Jiang,Yingjiang Ye,Zhanlong Shen,Boxi Kang,Yichao Yan,Xinmei Huang,Shan Wang

doi:10.21147/j.issn.1000-9604.2019.03.12

Abstract

ObjectiveCurrently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G (IgG) is widely expressed in many cancers, and it promotes cancer progression. This study explored the role of cancer-derived IgG (CIgG) in colorectal cancer.MethodsFirst, using a monoclonal antibody to CIgG, we examined the expression levels of CIgG in colorectal cancer cell lines by western blot and immunofluorescence analyses and in tissue specimens by immunohistochemistry. Second, the variable region gene was amplified by nested polymerase chain reaction (PCR), and PCR products were sequenced and analyzed. Third, we investigated the effect of CIgG on colorectal cancer cells by cell proliferation, wound healing, migration and invasion assays, and colony formation assay. Fourth, we performed in vivo tumorigenicity experiments to explore the effect of CIgG on tumorigenicity. Finally, we used RNA-seq analysis and co-immunoprecipitation experiments to further clarify possible mechanisms of CIgG. ResultsWe found that CIgG is widely expressed in colorectal cancer cells, and the overexpression of CIgG indicates significantly poor colorectal cancer prognosis. Furthermore, CIgG knockdown significantly inhibits the proliferation, migration and invasion ability of cells, and tumor growth in vivo. RNA-seq analysis indicated that CIgG knockdown results primarily in changes in expression of apical junction and epithelial-mesenchymal transition-related genes. CIgG may be involved in colorectal cancer invasion and metastasis through interacting with E-cadherin. ConclusionsCIgG is a potential human oncogene in colorectal cancer and that it has potential for application as a novel target in targeted therapy and a marker for prognostic evaluation.

Highlights

Colorectal cancer, one of the most common types of cancer, has the third highest incidence rate and the fourth highest mortality rate worldwide [1]
The results revealed that cancer-derived IgG (CIgG) was mainly distributed within the cancer nest of cancer tissues, whereas commercial anti-Immunoglobulin G (IgG) recognized both cancer cells and stromal cells of colorectal tissues (Figure 1A)
We found that CH1-related glycosylated CIgG was mainly distributed in the cancer nest of cancer www.cjcrcn.org tissues (55/100, 55%) compared with that in normal tissues adjacent to cancer tissues (6/80, 7.5%)

Summary

Introduction

Colorectal cancer, one of the most common types of cancer, has the third highest incidence rate and the fourth highest mortality rate worldwide [1]. Chin J Cancer Res 2019;31(3):499510 patients with colorectal cancer remains unsatisfactory. New clinical treatments for colorectal cancer are urgently needed. Tumor immunotherapy has shown great promise, but immunotherapy, especially immunocytotherapy, depends on the availability of specific targets on tumors. At present, there is no effective specific target for immunocytotherapy or targeted therapy in colorectal cancer. Molecular markers such as carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125 and CA19-9 have been widely used in clinical diagnosis and prognostic evaluation, no markers are available to provide critical information for the early diagnosis and management of colorectal cancer patients [4,5]. New molecular markers must be identified as a supplement to the current markers

Methods

Results

Conclusion