Background Non-small cell lung cancer (NSCLC) is the major type of lung cancer with high morbidity and poor prognosis. Erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), has been clinically applied for NSCLC treatment. Nevertheless, the erlotinib acquired resistance of NSCLC occurs inevitably in recent years. Methods Through analyzing two microarray datasets, erlotinib resistant NSCLC cells microarray (GSE80344) and NSCLC tissue microarray (GSE19188), the differentially expressed genes (DEGs) were screened via R language. DEGs were then functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, which up-regulated more than 2-folds in both datasets were further functionally analyzed by Oncomine, GeneMANIA, R2, Coremine, and FunRich. Results We found that matrix metalloproteinase 1 (MMP1) may confer the erlotinib therapeutic resistance in NSCLC. MMP1 highly expressed in erlotinib-resistant cells and NSCLC tissues, and it associated with poor overall survival. In addition, MMP1 may be associated with COPS5 and be involve in an increasing transcription factors HOXA9 and PBX1 in erlotinib resistance. Conclusions Generally, these results demonstrated that MMP1 may play a crucial role in erlotinib resistance in NSCLC, and MMP1 could be a prognostic biomarker for erlotinib treatment.

中文翻译：

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基于生物信息学分析鉴定 MMP1 作为赋予非小细胞肺癌厄洛替尼耐药性的潜在基因

背景非小细胞肺癌（NSCLC）是肺癌的主要类型，发病率高，预后差。厄洛替尼是一种表皮生长因子受体（EGFR）抑制剂，已在临床上应用于非小细胞肺癌的治疗。尽管如此，厄洛替尼对非小细胞肺癌的获得性耐药是近年来不可避免的。方法通过分析厄洛替尼耐药NSCLC细胞芯片（GSE80344）和NSCLC组织芯片（GSE19188）两个芯片数据集，通过R语言筛选差异表达基因（DEGs）。然后通过基因本体论 (GO) 分析和京都基因和基因组百科全书 (KEGG) 分析对 DEG 进行功能注释，在两个数据集中上调超过 2 倍，并通过 Oncomine、GeneMANIA、R2、Coremine 和乐富。结果我们发现基质金属蛋白酶1 (MMP1) 可能赋予厄洛替尼治疗NSCLC 的耐药性。MMP1 在厄洛替尼耐药细胞和 NSCLC 组织中高表达，并且与较差的总生存率相关。此外，MMP1 可能与 COPS5 相关，并在厄洛替尼耐药中参与增加转录因子 HOXA9 和 PBX1。结论 总的来说，这些结果表明 MMP1 可能在 NSCLC 的厄洛替尼耐药中起关键作用，并且 MMP1 可能是厄洛替尼治疗的预后生物标志物。MMP1 可能与 COPS5 相关，并在厄洛替尼耐药中参与增加转录因子 HOXA9 和 PBX1。结论 总的来说，这些结果表明 MMP1 可能在 NSCLC 的厄洛替尼耐药中起关键作用，并且 MMP1 可能是厄洛替尼治疗的预后生物标志物。MMP1 可能与 COPS5 相关，并在厄洛替尼耐药中参与增加转录因子 HOXA9 和 PBX1。结论 总的来说，这些结果表明 MMP1 可能在 NSCLC 的厄洛替尼耐药中起关键作用，并且 MMP1 可能是厄洛替尼治疗的预后生物标志物。