Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Department of Rehabilitation, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
Gene. 2018 Jul 30;665:57-66. doi: 10.1016/j.gene.2018.04.066. Epub 2018 Apr 24.
Lung cancer leads to the largest number of cancer-related deaths worldwide and is usually accompanied with metastasis which is the primary cause of those death and correlated with poor prognosis. However, the mechanism of lung cancer metastasis is still lack of definition.
We compared the primary lung adenocarcinoma (AD) and its metastasis tissues induced by overexpression of Kras and inactivation of P53 in mouse lungs by analyzing GSE40222 about the differentially expressed genes (DEGs), pathways and hub genes. And human lung AD databases are used to verify the conversed changes of identified key gene and then followed functional studies are performed to explore the functions of key gene.
We identified 165 genes differentially expressed in lung AD metastasis compared to primary AD. Pathway analysis identified 649 GO biological processes and 8 KEGG pathways, such as ECM-receptor interaction. Biological network interaction identified the hub genes during lung adenocarcinoma metastasis, such as the up-regulated COL5A1, a novel gene in AD metastasis. We found it's also increased in human AD and advanced stage. Knockdown of COL5A1 in human AD metastatic cells inhibited cell growth and invasion, and induced cell apoptosis. Notably, higher expression of COL5A1 was observed in the lung AD patients with recurrence and short survive.
By analyzing mouse lung AD and its metastases, we identified the potential key genes and pathways regulating lung AD metastasis, such as COL5A1. The following analysis of COL5A1 in human AD database and cells explores its functions, holding the implications of target therapy in AD metastasis and also providing more clues for future studies.
肺癌是全球癌症相关死亡人数最多的癌症，通常伴有转移，这是导致死亡的主要原因，与预后不良相关。然而，肺癌转移的机制仍不明确。
我们通过分析 GSE40222 中小鼠肺部过表达 Kras 和失活 P53 诱导的原发性肺腺癌（AD）及其转移组织中的差异表达基因（DEGs）、途径和枢纽基因，比较了原发性肺 AD 和其转移组织。并使用人类肺 AD 数据库验证鉴定的关键基因变化的一致性，然后进行功能研究以探索关键基因的功能。
我们在肺 AD 转移与原发性 AD 相比，鉴定出 165 个差异表达的基因。途径分析确定了 649 个 GO 生物过程和 8 个 KEGG 途径，如 ECM-受体相互作用。生物网络相互作用确定了肺腺癌转移过程中的枢纽基因，如上调的 COL5A1，这是 AD 转移中的一个新基因。我们发现它在人类 AD 和晚期也增加了。在人 AD 转移性细胞中敲低 COL5A1 抑制细胞生长和侵袭，并诱导细胞凋亡。值得注意的是，在肺 AD 患者复发和存活时间较短的患者中观察到 COL5A1 的表达更高。
通过分析小鼠肺 AD 及其转移，我们鉴定出调节肺 AD 转移的潜在关键基因和途径，如 COL5A1。随后对 COL5A1 在人类 AD 数据库和细胞中的分析探讨了其功能，为 AD 转移的靶向治疗提供了依据，并为未来的研究提供了更多线索。
