Li Dong, Xing Ying, Tian Tiannv, Guo Yanan, Qian Jing
Department of Thoracic Surgery, Huzhou Central Hospital, Huzhou, Zhejiang, People's Republic of China.
Department of Gastroenterology, The 72nd Army Hospital of the People's Liberation Army of China, Huzhou, Zhejiang, People's Republic of China.
Onco Targets Ther. 2020 Jul 3;13:6453-6463. doi: 10.2147/OTT.S245336. eCollection 2020.
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.
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.
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.
LRRC59 may serve as a novel biomarkers and therapeutic target for LUAD clinical practice.
富含亮氨酸重复序列蛋白59(LRRC59)是一种核糖体结合蛋白,也可与成纤维细胞生长因子相互作用。有限的研究揭示了LRRC59在乳腺癌侵袭性表型中可能发挥的作用。然而,LRRC59是否促进肺癌进展仍不清楚。
在本研究中,使用基于癌症基因组图谱(TCGA)的在线生存分析软件(GEPIA2)评估LRRC59 mRNA表达水平对肺癌的预后价值。采用细胞计数试剂盒-8法、集落形成试验、细胞周期分析和Transwell试验评估LRRC59在肺癌细胞中的生物学功能。然后,收集94例肺腺癌(LUAD)患者组织,通过基于组织芯片(TMA)的免疫组织化学染色(IHC)检测LRRC59的表达水平。进行单因素Kaplan-Meier分析和多因素Cox回归分析,以评估LRRC59蛋白表达在LUAD中的预后价值。
LRRC59的mRNA水平较高与肺腺癌患者较差的生存率显著相关,但与肺鳞状细胞癌无关。通过短发夹RNA(shRNA)敲低LRRC59明显抑制了H1299和A549细胞的增殖和集落形成。在A549和H1299细胞中观察到LRRC59缺失诱导的G1/S期阻滞。此外,LRRC59的沉默降低了细胞的迁移和侵袭能力。此外,基于TMA的IHC显示,LRRC59在LUAD组织中高表达,且与淋巴结转移(P<0.001)、TNM分期(P<0.001)和组织学分化(P=0.007)密切相关。进一步的多因素分析表明,LRRC59过表达是LUAD的独立预后因素。
LRRC59可能作为LUAD临床实践中的一种新型生物标志物和治疗靶点。