Identification of TIMELESS and RORA as key clock molecules of non-small cell lung cancer and the comprehensive analysis.
Identification of TIMELESS and RORA as key clock molecules of non-small cell lung cancer and the comprehensive analysis.
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TIMELESS和RORA作为非小细胞肺癌关键时钟分子的鉴定及综合分析
DOI：
10.1186/s12885-022-09203-1
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发表时间：
2022-01-25
期刊：
影响因子：
3.8
通讯作者：
Pan Y
中科院分区：
文献类型：
--
作者：
Xian H;Li Y;Zou B;Chen Y;Yin H;Li X;Pan Y
全球范围内非小细胞肺癌（NSCLC）的发病率一直在上升，最近越来越多的证据表明昼夜节律紊乱与癌症风险增加和预后较差之间存在相关性。另一方面，耐药性和肿瘤异质性的影响在NSCLC治疗中是不可避免的。这些都导致迫切需要为非小细胞肺癌的诊断和治疗找到更有用的预后和预测标志物，特别是在生物钟基因方面。使用 TIMER 和 Oncomine 数据库探讨了癌症中主要时钟基因的表达。通过对 TCGA 数据库样本的 Kaplan-Meier 估计和 Cox 回归系统地探讨了关键时钟基因的预后价值。对患者组织样本进行 RT-qPCR，以进一步验证数据库的结果。使用“ClusterProfiler”R包进行功能富集分析，并使用TIDE、TIMER2.0和XCELL等多种算法评估关键时钟基因与肿瘤突变负荷、免疫检查点和免疫浸润水平的相关性。 TIMELESS 在临床肺癌患者肺组织以及 TCGA 和 Oncomine 数据库中显着上调，而 RORA 下调。多变量Cox回归分析表明，TIMELESS（P = 0.004，HR = 1.21 [1.06，1.38]）和RORA（P = 0.047，HR = 0.868 [0.755，0.998]）与NSCLC的总生存率显着相关。 TIMELESS相关基因在细胞周期和免疫系统中富集，RORA的功能主要集中在致癌信号通路或糖基化和蛋白质激活上。此外，TIMELESS 与肿瘤突变负荷呈正相关，而 RORA 与之呈负相关。 TIMELESS 和 RORA 也与 NSCLC 中的免疫检查点和免疫浸润水平显着相关。此外，TIMELESS 与脂质代谢呈显着正相关。 TIMELESS 和 RORA 被确定为 NSCLC 中的关键时钟基因，并且是 NSCLC 总生存率的独立预后因素。对它们的功能进行了多方面的评估，表明这两个基因作为 NSCLC 进展和预后的生物标志物的强大潜力。在线版本包含可在 10.1186/s12885-022-09203-1 获取的补充材料。
The incidence rate of non-small cell lung cancer (NSCLC) has been increasing worldwide, and the correlation of circadian rhythm disruption with a raised risk of cancer and worse prognosis has been shown by accumulating evidences recently. On the other hand, drug resistance and the impact of tumor heterogeneity have been inevitable in NSCLC therapy. These both lead to an urgent need to identify more useful prognostic and predictive markers for NSCLC diagnosis and treatment, especially on the aspect of circadian clock genes. The expression of the main clock genes in cancer was probed with TIMER and Oncomine databases. The prognostic value of key clock genes was probed systematically with the Kaplan–Meier estimate and Cox regression on samples from TCGA database. RT-qPCR was performed on patient tissue samples to further validate the results from databases. The functional enrichment analysis was performed using the “ClusterProfiler” R package, and the correlation of key clock genes with tumor mutation burden, immune checkpoint, and immune infiltration levels were also assessed using multiple algorithms including TIDE, TIMER2.0, and XCELL. TIMELESS was significantly upregulated in lung tissue of clinical lung cancer patients as well as TCGA and Oncomine databases, while RORA was downregulated. Multivariate Cox regression analysis indicated that TIMELESS (P = 0.004, HR = 1.21 [1.06, 1.38]) and RORA (P = 0.047, HR = 0.868 [0.755, 0.998]) has a significant correlation with overall survival in NSCLC. Genes related to TIMELESS were enriched in the cell cycle and immune system, and the function of RORA was mainly focused on oncogenic signaling pathways or glycosylation and protein activation. Also, TIMELESS was positively correlated with tumor mutation burden while RORA was negatively correlated with it. TIMELESS and RORA were also significantly correlated with immune checkpoint and immune infiltration levels in NSCLC. Additionally, TIMELESS showed a significant positive relationship with lipid metabolism. TIMELESS and RORA were identified as key clock genes in NSCLC, and were independent prognostic factors for overall survival in NSCLC. The function of them were assessed in many aspects, indicating the strong potential of the two genes to serve as biomarkers for NSCLC progression and prognosis. The online version contains supplementary material available at 10.1186/s12885-022-09203-1.
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作者：
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影响因子：
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作者：
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通讯作者：
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