Abstract
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.
Highlights
Breast cancer (BC) is the leading cause of cancer and the most common cancer in women worldwide, affecting approximately 12% of females during their lifetimes [1]
The high expression of immunoglobulin lambda constant 2 (IGLC2) was exhibited in the basal-like immune-activated (BLIA) triple-negative breast cancer (TNBC) molecular subtype, which was immune-activated and showed excellent response to immune therapy
The results of pathway enrichment analysis showed that IGLC2 is related to the phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and extracellular matrix–receptor interaction
Summary
Breast cancer (BC) is the leading cause of cancer and the most common cancer in women worldwide, affecting approximately 12% of females during their lifetimes [1]. Triple-negative BC (TNBC) is a subtype of BC that lacks the expression of ER, PR, and HER-2, is generally aggressive, has high rates of relapse, and results in a decreased overall survival [3, 4]. TNBC accounts for 10%–20% of all BCs [5]. Given that TNBC lacks the expression of ER/PR/HER2, the application of endocrine therapy or targeted therapy against HER2 is difficult. Immunoglobulin-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
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