A Novel IGLC2 Gene Linked With Prognosis of Triple-Negative Breast Cancer

Frontiers in Oncology

Chien-Yi Yang¹  Huan-Ming Hsu¹  Yu-Jia Chang⁴  Meng-Chiung Lin⁶  Chi-Ming Chu^1,10  Vincent S. Tseng^1,11  Wen-Chiuan Tsai^1,12  Guo-Shiou Liao^1,14  Jyh-Cherng Yu^1,14  Chia-Chao Wu^1,15  Wei-Zhi Lin^1,16  Je-Ming Hu^1,18  Yu-Tien Chang^1,19 

[1] 0Department of Surgery, Songshan Branch of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;2Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;3Cancer Research Center and Translational Laboratory, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan;4Division of Gastroenterology, Department of Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan;5Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan;6Division of Biostatistics and Informatics, Department of Epidemiology, School of Public Health, National Defense Medical Center, Taipei, Taiwan;7Big Data Research Center, Fu-Jen Catholic University, New Taipei City, Taiwan;8Department of Public Health, China Medical University, Taichung, Taiwan;9Department of Healthcare Administration and Medical Informatics College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan;Department of Computer Science, National Chiao Tung University, Hsinchu, Taiwan;Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital,National Defense Medical Center, Taipei, Taiwan;Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;School of Medicine, National Defense Medical Center, Taipei, Taiwan;School of Public Health, National Defense Medical Center, Taipei, Taiwan;

关键词: immunoglobulin;    breast cancer;    triple-negative breast cancer (TNBC);    MDA-MB-231;    prognosis;    next-generation sequencing;   

DOI  :  10.3389/fonc.2021.759952

来源: DOAJ

【 摘 要 】

BackgroundImmunoglobulin-related genes are associated with the favorable prognosis of triple-negative breast cancer (TNBC) patients. We aimed to analyze the function and prognostic value of immunoglobulin lambda constant 2 (IGLC2) in TNBC patients.MethodsWe knocked down the gene expression of IGLC2 (IGLC2-KD) in MDA-MB-231 cells to evaluate the proliferation, migration, and invasion of tumors via 3-(4,5-Dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, wound healing, and transwell cell migration assay respectively. Relapse-free survival (RFS) and distant metastasis-free survival (DMFS) analyses were conducted using the KM plotter online tool. The GSE76275 data set was used to analyze the association of IGLC2 and clinical characteristics. A pathway enrichment analysis was conducted using the next-generation sequencing data of wild-type and IGLC2-KD MDA-MB-231 cells.ResultsThe low gene expression of IGLC2 was related to unfavorable RFS, DMFS. The high expression of IGLC2 was exhibited in the basal-like immune-activated (BLIA) TNBC molecular subtype, which was immune-activated and showed excellent response to immune therapy. IGLC2 was positively correlated with programmed death-ligand 1 (PD-L1) as shown by Spearman correlation (r = 0.25, p < 0.0001). IGLC2 had a strong prognostic effect on lymph node-negative TNBC (RFS range: 0.31, q value= 8.2e-05; DMFS = 0.16, q value = 8.2e-05) but had no significance on lymph node-positive ones. The shRNA-mediated silencing of IGLC2 increased the proliferation, migration, and invasion of MDA-MB-231 cells. The results of pathway enrichment analysis showed that IGLC2 is related to the PI3K-Akt signaling pathway, MAPK signaling pathway, and extracellular matrix–receptor interaction. We confirmed that MDA-MB-231 tumor cells expressed IGLC2, subverting the traditional finding of generation by immune cells.ConclusionsIGLC2 linked with the proliferation, migration, and invasion of MDA-MB-231 cells. A high expression of IGLC2 was related to favorable prognosis for TNBC patients. IGLC2 may serve as a biomarker for the identification of TNBC patients who can benefit the most from immune checkpoint blockade treatment.

【 授权许可】

Unknown