OncoTargets and Therapy (Jul 2020)
Overexpression of LRRC59 Is Associated with Poor Prognosis and Promotes Cell Proliferation and Invasion in Lung Adenocarcinoma
Abstract
Dong Li,1,* Ying Xing,2,* Tiannv Tian,3 Yanan Guo,3 Jing Qian3,4 1Department of Thoracic Surgery, Huzhou Central Hospital, Huzhou, Zhejiang, People’s Republic of China; 2Department of Gastroenterology, The 72nd Army Hospital of the People’s Liberation Army of China, Huzhou, Zhejiang, People’s Republic of China; 3Huzhou University Schools of Nursing and Medicine, Huzhou University, Huzhou, Zhejiang, People’s Republic of China; 4Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing QianHuzhou University Schools of Nursing and Medicine, Huzhou University, Huzhou, Zhejiang Province 313000, People’s Republic of ChinaTel +8613905723707Email [email protected]: 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, proliferation, metastasis, prognosis
