Overexpression of LRRC59 Is Associated with Poor Prognosis and Promotes Cell Proliferation and Invasion in Lung Adenocarcinoma

Onco Targets Ther. 2020 Jul 3:13:6453-6463. doi: 10.2147/OTT.S245336. eCollection 2020.

Abstract

Aim: LRRC59 (leucine-rich repeat-containing protein 59) is a ribosome-binding protein that also interacts with fibroblast growth factors. Limited investigations revealed a possible role of LRRC59 in the aggressive phenotype of breast cancer. However, whether LRRC59 contributes to the progression of lung cancer remains unclear.

Materials and methods: In this study, an online TCGA-based survival analysis software (GEPIA2) was used to estimate the prognostic value of LRRC59 mRNA expression level for lung cancer. Cell Counting Kit-8 assay, colony-forming assay, cell cycle analysis, and transwell assay were used to assess the biological functions of LRRC59 in lung cancer cells. Then, 94 lung adenocarcinoma (LUAD) patient tissues were collected to examine the expression level of LRRC59 by the tissue microarray (TMA)-based immunohistochemistry staining (IHC). Univariate Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the prognostic value of LRRC59 protein expression in LUAD.

Results: Higher mRNA level of LRRC59 was significantly associated with worse survival for lung adenocarcinoma, but not for lung squamous cell carcinoma. Knockdown of LRRC59 by shRNA apparently inhibited cell proliferation and colony formation in both H1299 and A549 cells. The G1/S phase arrest induced by LRRC59 depletion was observed in A549 and H1299 cells. Besides, the silencing of LRRC59 decreased cell migrative and invasive abilities. Moreover, TMA-based IHC showed that LRRC59 was highly expressed in LUAD tissues and closely associated with lymph node metastasis (P<0.001), TNM stage (P<0.001), and histological differentiation (P=0.007). Further multivariate analysis suggested that LRRC59 overexpression was an independent prognostic factor in LUAD.

Conclusion: LRRC59 may serve as a novel biomarkers and therapeutic target for LUAD clinical practice.

Keywords: LRRC59; lung adenocarcinoma; metastasis; prognosis; proliferation.