Kędzia Konrad, Szmajda-Krygier Dagmara, Krygier Adrian, Jabłoński Sławomir, Balcerczak Ewa, Wcisło Szymon
Department of Thoracic, General and Oncological Surgery, Medical University of Lodz and Military Medical Academy Memorial Teaching Hospital of the Medical University of Lodz-Central Veteran Hospital, Lodz, Poland.
Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Lodz, Poland.
Transl Lung Cancer Res. 2024 Nov 30;13(11):2903-2917. doi: 10.21037/tlcr-24-448. Epub 2024 Nov 5.
Despite the decrease of morbidity rate of non-small cell lung cancer (NSCLC) in recent years, it is still a cancer with poor prognosis. Lung cancers (LCs) are usually diagnosed at a late stage of the disease due to non-specific clinical symptoms. Proper regulation of carnitine levels is important in the context of development and increased risk of cancer cells proliferation. The expression profiles and clinical value of family members in LC remain largely unexplored. The aim of the study was the assessment of , and mRNA expression level among patients suffering from NSCLC. The obtained results were compared with the clinical and the pathological features of NSCLC patients.
Through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and bioinformatics studies, the evaluation of carnitine transporting genes (, and ) mRNA levels was performed in order to elucidate their connection to clinical features of patients and influence on overall survival (OS).
The analysis showed a significant difference for the gene of NSCLC patients and for and genes in LUSC patients in terms of sex (P=0.002, P=0.02 and P=0.001, respectively) and in terms of tobacco smoking (P=0.04). Analysis also revealed a significant negative correlation for and genes expression level in the lung adenocarcinoma (LUAD) subtype with standardized uptake value (SUV) (r=-0.40, P=0.02 and r=-0.43, P=0.04). The significant downregulation of gene expression compared to normal adjacent tissue was observed for in lung squamous cell carcinoma (LUSC) and for in both LUAD and LUSC subtypes. The effect of the , and gene expression at the time of diagnosis on the OS time of LC patients revealed that lower expression correlated with a shorter 5 years OS (all P values <0.01). The effects were distinct after division for LUAD and LUSC subtypes.
The expression levels of genes encoding carnitine transporters are diverse, hinting at a potentially altered carnitine metabolism in LC patients. Notably, this variance is not uniform and exhibits specificity across LC subtypes, with marked distinctions between LUAD and LUSC. The correlation between gene expression levels and OS of patients underlines the prognostic significance of genes within these cancer subtypes.
尽管近年来非小细胞肺癌（NSCLC）的发病率有所下降，但它仍然是一种预后较差的癌症。由于临床症状不具特异性，肺癌（LC）通常在疾病晚期才被诊断出来。在癌细胞增殖的发展和风险增加的背景下，肉碱水平的适当调节很重要。LC中相关家族成员的表达谱和临床价值在很大程度上仍未得到探索。本研究的目的是评估非小细胞肺癌患者中[相关基因名称1]、[相关基因名称2]和[相关基因名称3]的mRNA表达水平。将获得的结果与非小细胞肺癌患者的临床和病理特征进行比较。
通过逆转录定量聚合酶链反应（RT-qPCR）和生物信息学研究，对肉碱转运基因（[相关基因名称1]、[相关基因名称2]和[相关基因名称3]）的mRNA水平进行评估，以阐明它们与患者临床特征的联系以及对总生存期（OS）的影响。
分析显示，非小细胞肺癌患者的[相关基因名称1]基因以及肺鳞癌（LUSC）患者的[相关基因名称2]和[相关基因名称3]基因在性别方面存在显著差异（分别为P = 0.002、P = 0.02和P = 0.001），在吸烟方面也存在显著差异（P = 0.04）。分析还显示，肺腺癌（LUAD）亚型中[相关基因名称2]和[相关基因名称3]基因的表达水平与标准化摄取值（SUV）之间存在显著负相关（r = -0.40，P = 0.02；r = -0.43，P = 0.04）。在肺鳞癌（LUSC）中观察到[相关基因名称1]基因表达与正常相邻组织相比显著下调，在肺腺癌（LUAD）和肺鳞癌（LUSC）亚型中均观察到[相关基因名称3]基因表达下调。诊断时[相关基因名称1]、[相关基因名称2]和[相关基因名称3]基因表达对肺癌患者总生存期的影响表明，较低的表达与较短的5年总生存期相关（所有P值<0.01）。在分为肺腺癌（LUAD）和肺鳞癌（LUSC）亚型后，影响有所不同。
编码肉碱转运蛋白的基因表达水平各不相同，这表明肺癌患者的肉碱代谢可能发生了改变。值得注意的是，这种差异并不一致，并且在肺癌亚型中表现出特异性，肺腺癌（LUAD）和肺鳞癌（LUSC）之间存在明显差异。基因表达水平与患者总生存期之间的相关性强调了这些癌症亚型中[相关基因名称1]、[相关基因名称2]和[相关基因名称3]基因的预后意义。
