Derakhshan Nazari Mohammad Hossein, Askari Dastjerdi Rana, Ghaedi Talkhouncheh Parnian, Bereimipour Ahmad, Mollasalehi Hamidreza, Mahshad Amir Ali, Razi Ali, Nazari Mohammad Hossein, Ebrahimi Sadrabadi Amin, Taleahmad Sara
Department of Microbiology and Microbial Biotechnology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Department of Cell and Molecular Biology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Cell J. 2022 Jun;24(6):302-308. doi: 10.22074/cellj.2022.7930. Epub 2022 Jun 29.
Non-small cell lung adenocarcinoma (NSCLC) is the most common type of lung cancer, which is considered as the most lethal and prevalent cancer worldwide. Recently, molecular changes have been implicated to play a significant role in the cancer progression. Despite of numerous studies, the molecular mechanism of NSCLC pathogenesis in each sub-stage remains unclear. Studying these molecular alterations gives us a chance to design successful therapeutic plans which is aimed in this research.
In this bioinformatics study, we compared the expression profile of 7 minor stages of NSCLC adenocarcinoma, including GSE41271, GSE42127, and GSE75037, to clarify the relation of molecular alterations and tumorigenesis. At first, 99 common differentially expressed genes (DEG) were obtained. Then, functional enrichment analysis and protein-protein interaction (PPI) network construction were performed to uncover the association of significant cellular and molecular changes. Finally, gene expression profile interactive analysis (GEPIA) was employed to validate the results by RNA-seq expression data.
Primary analysis showed that was downregulated through the tumor progression to the stage IB and was upregulated in the course of final tumor development to the stage IV and distant metastasis. Functional enrichment analysis indicated that in the TGF-β signaling pathway and in the glutathione metabolism pathway may be the key genes for NSCLC adenocarcinoma progression. GEPIA analysis revealed a correlation between downregulation and upregulation and lung adenocarcinoma (LUAD) progression and lower survival chances in LUAD patients which confirm microarray data.
Taken together, we suggested as an oncogene by inhibiting apoptosis, promoting EMT and increasing glucose uptake in the final stages and BMP4 as a tumor suppressor via inducing apoptosis and arresting cell cycle in the early stages through lung adenocarcinoma (ADC) development to make them candidate genes to further cancer therapy investigations.
非小细胞肺腺癌（NSCLC）是最常见的肺癌类型，被认为是全球最致命且流行的癌症。最近，分子变化被认为在癌症进展中起重要作用。尽管有大量研究，但NSCLC发病机制在每个亚阶段的分子机制仍不清楚。研究这些分子改变为我们设计成功的治疗方案提供了机会，这也是本研究的目标。
在这项生物信息学研究中，我们比较了NSCLC腺癌7个微小阶段的表达谱，包括GSE41271、GSE42127和GSE75037，以阐明分子改变与肿瘤发生的关系。首先，获得了99个常见的差异表达基因（DEG）。然后，进行功能富集分析和蛋白质-蛋白质相互作用（PPI）网络构建，以揭示显著的细胞和分子变化之间的关联。最后，采用基因表达谱交互分析（GEPIA）通过RNA测序表达数据验证结果。
初步分析表明，在肿瘤进展到IB期时下调，在最终肿瘤发展到IV期和远处转移过程中上调。功能富集分析表明，TGF-β信号通路中的 和谷胱甘肽代谢通路中的 可能是NSCLC腺癌进展的关键基因。GEPIA分析揭示了 下调和 上调与肺腺癌（LUAD）进展以及LUAD患者较低的生存机会之间的相关性，这证实了微阵列数据。
综上所述，我们认为 在肺癌腺癌（ADC）发展的最后阶段通过抑制凋亡、促进上皮-间质转化（EMT）和增加葡萄糖摄取而作为癌基因，而BMP4在早期阶段通过诱导凋亡和阻止细胞周期而作为肿瘤抑制因子，使其成为进一步癌症治疗研究的候选基因。
