The correlation and role analysis of COL4A1 and COL4A2 in hepatocarcinogenesis

被引:39
作者
Liu, Yanli [1 ,2 ]
Zhang, Jiaye [4 ,5 ]
Chen, Yan [4 ,5 ]
Sohel, Hasan [4 ,5 ]
Ke, Xinrong [1 ,2 ]
Chen, Jingqi [1 ,2 ,3 ]
Li, Yin-Xiong [4 ,5 ,6 ,7 ,8 ]
机构
[1] Guangzhou Med Univ, Affiliated Hosp 2, Stem Cell Translat Med Ctr, State Key Lab Resp Dis, Guangzhou, Peoples R China
[2] Guangzhou Med Univ, Affiliated Hosp 2, Stem Cell Translat Med Ctr, Guangzhou, Peoples R China
[3] Guangzhou Med Univ, Dept Med Oncol, Guangzhou, Peoples R China
[4] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Inst Publ Hlth, Guangzhou, Peoples R China
[5] Chinese Acad Sci, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed & Hlth, Key Lab Regenerat Biol, Guangzhou, Peoples R China
[6] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Biocomp, Guangzhou, Peoples R China
[7] Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou, Peoples R China
[8] Univ Chinese Acad Sci, Beijing, Peoples R China
来源
AGING-US | 2020年 / 12卷 / 01期
关键词
tumor microenvironment; COL4A1/A2; HCC; PI-3K pathway; PTK2; SERUM RESPONSE FACTOR; FOCAL ADHESION KINASE; HEPATOCELLULAR-CARCINOMA HCC; GENE-EXPRESSION; CANCER; MARKER; SORAFENIB; SURVIVAL; IV; MICROENVIRONMENT;
D O I
10.18632/aging.102610
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Liver fibrosis biomarker, Type IV collagen, may function as hepatocarcinogenesis niche. However, among the six isoforms, the isoforms providing tumor microenvironment and their regulatory network are still unclarified. Based on bioinformatics analysis of hundreds of HCC transcriptome datasets from public databases, we found that COL4A1/2 expressions were significantly correlated with hepatocarcinogenesis, progression, and prognosis. The expressions of COL4A1/2 were significantly upregulated in the preneoplastic and HCC tissues compared with normal tissues. Moreover, the overexpression of COL4A2 was highly correlated with shorter progression-free survival in HCC patients. Bioinformatics analysis also generates an interactive regulatory network in which COL4A1/2 directly binding to integrin alpha-2/beta-1 initiates a sequentially and complicated signaling transduction, to accelerate cell cycle and promote tumorigenesis. Among those pathways, the PI3K-Akt pathway is significantly enriched in cooperative mutations and correlation analysis. This suggests that the key activated signaling is PI3K-Akt pathway which severing as the centerline linked with other pathways (Wnt and MAPK signaling) and cell behaviors signaling (cell cycle control and cytoskeleton change). Switching extracellular matrix collagen isoform may establish pro-tumorigenic and metastatic niches. The findings of COL4A1/2 and related signaling networks are valuable to be further investigated that may provide druggable targets for HCC intervention.
引用
收藏
页码:204 / 223
页数:20
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