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非小细胞肺癌中代谢相关基因及CRLS1的表达与潜在机制

Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.

作者信息

Feng Hai-Ming, Zhao Ye, Zhang Jian-Ping, Zhang Jian-Hua, Jiang Peng, Li Bin, Wang Cheng

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.

The Evidence Based Medicine Center of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):2661-2668. doi: 10.3892/ol.2017.7591. Epub 2017 Dec 12.

Abstract

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.

摘要

心磷脂(CL)是一种定位于线粒体的磷脂,对线粒体结构和功能至关重要。人的心磷脂合酶1(CRLS1)在调节磷脂酰甘油(PG)重塑和CL生物合成中起重要作用。然而,CRLS1在包括非小细胞肺癌(NSCLC)在内的肿瘤中的表达及独特的预后价值尚未明确。在本研究中,使用Oncomine分析研究了CRLS1的mRNA表达,并使用Kaplan-Meier绘图仪数据库评估了NSCLC患者的预后价值。分析结果表明,与正常肺组织相比,CRLS1在肺癌中的表达较低。值得注意的是,发现CRLS1高表达与所有NSCLC患者和肺腺癌(Ade)患者的总生存期(OS)改善相关。然而,在鳞状细胞癌(SCC)患者中未观察到这种情况。结果还表明,CRLS1的mRNA表达与NSCLC患者的临床病理参数相关,包括性别、吸烟状况、肿瘤分级、临床分期、淋巴结状况和化疗。这些结果表明,CRLS1与NSCLC患者的预后改善相关,尤其是在早期阶段(T1N1M0)。此外,使用基因本体术语富集分析表明,CRLS1与已知的代谢相关基因共表达。京都基因与基因组百科全书通路分析还表明,肿瘤相关代谢和丝裂原活化蛋白激酶(MAPK)信号通路富含CRLS1共表达基因。本研究结果表明,CRLS1可能是一种新型肿瘤抑制因子,参与调节肿瘤微环境中的脂质和硒氨基酸代谢,并在肿瘤发生和发展过程中抑制MAPK信号通路。对CRLS1的表达、预后和潜在机制进行综合评估可能有助于更好地理解NSCLC分子生物学的复杂性。

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