Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer
Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer
复制标题
DOI：
10.3892/ol.2017.7591
复制
发表时间：
2018-02-01
期刊：
影响因子：
2.9
通讯作者：
Wang, Cheng
中科院分区：
文献类型：
--
作者：
Feng, Hai-Ming;Zhao, Ye;Wang, Cheng
心磷脂（CL）是一种位于线粒体中的磷脂，对线粒体的结构和功能至关重要。人心磷脂合酶1（CRLS 1）在调节磷脂酰甘油（PG）重塑和CL生物合成中是重要的。然而，CRS 1在肿瘤（包括非小细胞肺癌（NSCLC））中的表达和独特的预后价值尚未得到充分确定。在本研究中，使用Oncomine分析研究CRLS1的mRNA表达，并使用Kaplan-Meier SPSS数据库评估NSCLC患者的预后价值。分析结果表明，肺癌组织中CRLS 1的表达低于正常肺组织。值得注意的是，在所有NSCLC和肺腺癌（Ade）患者中，发现CRLS1的高表达与总生存期（OS）改善相关。然而，这在鳞状细胞癌（SCC）患者中未观察到。结果还表明，CRLS 1的mRNA表达与NSCLC患者的临床病理参数，包括性别，吸烟状况，肿瘤分级，临床分期，淋巴结状态和化疗之间的相关性。这些结果表明，CRLS1与NSCLC患者的预后改善相关，特别是在早期（T1N1M0）。此外，使用基因本体学术语富集分析揭示了CRLS 1与与代谢相关的已知基因共表达。京都基因百科全书和基因组通路分析也显示，肿瘤相关代谢和丝裂原活化蛋白激酶（MAPK）信号通路中富含CRLS 1共表达基因。本研究结果提示，CRLS 1可能是一种新的肿瘤抑制因子，参与调节肿瘤微环境中的脂质和硒氨基酸代谢，抑制肿瘤发生发展过程中的MAPK信号通路。对CRLS1的表达、预后及可能机制进行综合评价，有助于进一步认识NSCLC分子生物学的复杂性。
Cardiolipin (CL) is a phospholipid localized in the mitochondria, which is essential for mitochondrial structure and function. Human cardiolipin synthase 1 (CRLS1) is important in regulating phosphatidylglycerol (PG) remodeling and CL biosynthesis. However, the expression and distinct prognostic value of CRLS1 in neoplasms, including non-small cell lung cancer (NSCLC), is not well established. In the present study, the mRNA expression of CRLS1 was investigated using Oncomine analysis and the prognostic value was assessed using the Kaplan-Meier plotter database for patients with NSCLC. The results of the analyses indicated that the expression of CRLS1 in lung cancer was lower, compared with that in normal lung tissues. Notably, a high expression of CRLS1 was found to be associated with improved overall survival (OS) in all patients with NSCLC and lung adenocarcinoma (Ade). However, this was not observed in patients with squamous cell carcinoma (SCC). The results also demonstrated an association between the mRNA expression of CRLS1 and the clinicopathological parameters of patients with NSCLC, including sex, smoking status, tumor grade, clinical stage, lymph node status and chemotherapy. These results indicated that CRLS1 was associated with improved prognosis in patients with NSCLC, particularly at an early stage (T1N1M0). In addition, it was revealed that CRLS1 was co-expressed with well-known genes associated with metabolism using Gene Ontology term enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed that tumor-related metabolism and the mitogen-activated protein kinase (MAPK) signaling pathways were enriched with CRLS1-co-expression genes. The results of the present study suggested that CRLS1 may be a novel tumor suppressor involved in regulating lipid and seleno-amino acid metabolism in the tumor microenvironment, and suppressing the MAPK signaling pathway during tumorigenesis and development. Comprehensive evaluation of the expression, prognosis and potential mechanism of CRLS1 is likely to promote an improved understanding of the complexity of the molecular biology of NSCLC.