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

被引：10

作者：

Chang, Yu-Tien ^{[1
]}

Tsai, Wen-Chiuan ^{[2
]}

Lin, Wei-Zhi ^{[3
]}

Wu, Chia-Chao ^{[4
]}

Yu, Jyh-Cherng ^{[5
]}

Tseng, Vincent S. ^{[6
]}

Liao, Guo-Shiou ^{[5
]}

Hu, Je-Ming ^{[7
,8
,9
]}

Hsu, Huan-Ming ^{[5
,10
]}

Chang, Yu-Jia ^{[11
,12
,13
,14
]}

Lin, Meng-Chiung ^{[15
,16
]}

Chu, Chi-Ming ^{[17
,18
,19
,20
]}

Yang, Chien-Yi ^{[10
]}

机构：

[1] Natl Def Med Ctr, Sch Publ Hlth, Taipei, Taiwan

[2] Triserv Gen Hosp, Dept Pathol, Natl Def Med Ctr, Taipei, Taiwan

[3] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan

[4] Triserv Gen Hosp, Div Nephrol, Dept Med, Natl Def Med Ctr, Taipei, Taiwan

[5] Triserv Gen Hosp, Div Gen Surg, Dept Surg, Natl Def Med Ctr, Taipei, Taiwan

[6] Natl Chiao Tung Univ, Dept Comp Sci, Hsinchu, Taiwan

[7] Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan

[8] Triserv Gen Hosp, Div Colorectal Surg, Dept Surg, Natl Def Med Ctr, Taipei, Taiwan

[9] Natl Def Med Ctr, Sch Med, Taipei, Taiwan

[10] Triserv Gen Hosp, Dept Surg, Songshan Branch, Natl Def Med Ctr, Taipei, Taiwan

[11] Taipei Med Univ, Grad Inst Clin Med, Coll Med, Taipei, Taiwan

[12] Taipei Med Univ, Wan Fang Hosp, Cell Physiol & Mol Image Res Ctr, Taipei, Taiwan

[13] Taipei Med Univ, Taipei Med Univ Hosp, Canc Res Ctr, Taipei, Taiwan

[14] Taipei Med Univ, Taipei Med Univ Hosp, Translat Lab, Taipei, Taiwan

[15] Taichung Armed Forces Gen Hosp, Dept Med, Div Gastroenterol, Taichung, Taiwan

[16] Natl Chiao Tung Univ, Dept Biol Sci & Technol, Hsinchu, Taiwan

[17] Natl Def Med Ctr, Div Biostat & Informat, Dept Epidemiol, Sch Publ Hlth, Taipei, Taiwan

[18] Fu Jen Catholic Univ, Big Data Res Ctr, New Taipei, Taiwan

[19] China Med Univ, Dept Publ Hlth, Taichung, Taiwan

[20] Kaohsiung Med Univ, Dept Healthcare Adm & Med Informat, Coll Hlth Sci, Kaohsiung, Taiwan

来源：

FRONTIERS IN ONCOLOGY | 2022年 / 11卷

关键词：

immunoglobulin; breast cancer; triple-negative breast cancer (TNBC); MDA-MB-231; prognosis; next-generation sequencing; relapse-free survival; distant metastasis-free survival; COEXPRESSION NETWORK; EXPRESSION PROFILES; IMMUNOGLOBULIN-G; CELL-LINES; IDENTIFICATION; SURVIVAL; THERAPY; GROWTH; CARDIOMYOPATHY; TRANSCRIPTOME;

D O I：

10.3389/fonc.2021.759952

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页数：15

共 92 条

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