Weibo Liu1, Haifeng Wei1, Zhengyu Gao2, Guanghui Chen1, Yujie Liu1, Xin Gao1, Guangjian Bai1, Shaohui He1, Tielong Liu1, Wei Xu3, Xinghai Yang4, Jian Jiao1, Jianru Xiao5. 1. Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. 2. Department of Rehabilitation, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China. 3. Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: davidxu_spine@smmu.edu.cn. 4. Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: cnspineyang@163.com. 5. Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: jianru_xiao12345@163.com.
Abstract
BACKGROUND: 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. METHODS: We compared the primary lung adenocarcinoma (AD) and its metastasis tissues induced by overexpression of KrasG12D 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: We compared the primary lung adenocarcinoma (AD) and its metastasis tissues induced by overexpression of KrasG12D and inactivation of P53 in mouse lungs by analyzing GSE40222 about the differentially expressed genes (DEGs), pathways and hub genes. And humanlung 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. RESULTS: 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 humanAD and advanced stage. Knockdown of COL5A1 in humanAD metastatic cells inhibited cell growth and invasion, and induced cell apoptosis. Notably, higher expression of COL5A1 was observed in the lung ADpatients with recurrence and short survive. CONCLUSION: By analyzing mouselung 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 humanAD database and cells explores its functions, holding the implications of target therapy in AD metastasis and also providing more clues for future studies.