OBJECTIVES Precision medicine with molecular profiling has revolutionized the management of lung cancer leading to improved outcomes. Patients with actionable mutations receive targeted therapy. As next-generation sequencing (NGS) becomes standard in lung cancer clinics, we sought to use molecular information to identify novel pathways to target in order to improve survival for non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS This retrospective analysis included 183 lung cancer patients who received commercial NGS sequencing as part of their clinical care, as well as the lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) dataset from the Cancer Genome Atlas (TCGA). We grouped mutations using a transcription factor enrichment analysis (TFEA), and the resulting TFEA groups were used to sort patients for survival analyses. RESULTS Mutations connected to transcription factor 7 like 2/ Transcription Factor 4 (TCF7L2/TCF4) were associated with poor survival in NSCLC patients. Furthermore, Mutations in CCND1, IDH1, SMARC4, and TP53 are the primary contributors to a poor prognosis in these patients. This four gene panel was also found to be associated with a poor prognosis in the LUAD data of TCGA dataset. CONCLUSIONS We determined that the TCF7L2 pathway is associated with a poor prognosis in patients with lung adenocarcinoma. Therefore, targeting the TCF7L2 pathway may improve outcomes for this group of patients.

中文翻译：

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与TCF7L2转录因子相关的基因突变与非小细胞肺癌的不良预后有关。

目的具有分子谱分析的精密医学彻底改变了肺癌的治疗方法，从而改善了治疗效果。具有可操作突变的患者接受靶向治疗。随着下一代测序（NGS）在肺癌临床中成为标准，我们寻求使用分子信息来确定靶向的新途径，以提高非小细胞肺癌（NSCLC）患者的生存率。材料与方法这项回顾性分析包括183名接受商业NGS测序作为其临床治疗一部分的肺癌患者，以及来自癌症基因组图谱（TCGA）的肺腺癌（LUAD）和鳞状细胞癌（LUSC）数据集。我们使用转录因子富集分析（TFEA）对突变进行了分组，然后将所得的TFEA组用于对患者进行分类以进行生存分析。结果与转录因子7（如2 /转录因子4（TCF7L2 / TCF4））相关的突变与NSCLC患者的不良生存率相关。此外，CCND1，IDH1，SMARC4和TP53的突变是这些患者预后不良的主要原因。还发现这四个基因组与TCGA数据集的LUAD数据的不良预后有关。结论我们确定TCF7L2途径与肺腺癌患者预后不良有关。因此，靶向TCF7L2途径可以改善该组患者的预后。CCND1，IDH1，SMARC4和TP53中的突变是这些患者预后不良的主要原因。还发现这四个基因组与TCGA数据集的LUAD数据的不良预后有关。结论我们确定TCF7L2途径与肺腺癌患者预后不良有关。因此，靶向TCF7L2途径可以改善该组患者的预后。CCND1，IDH1，SMARC4和TP53中的突变是这些患者预后不良的主要原因。还发现这四个基因组与TCGA数据集的LUAD数据的不良预后有关。结论我们确定TCF7L2途径与肺腺癌患者预后不良有关。因此，靶向TCF7L2途径可以改善该组患者的预后。