单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Cancer Biol Res Ctr,Key Lab,Minist Educ,Wuhan,Peoples R China肿瘤生物医学中心华中科技大学同济医学院附属同济医院妇产科学系妇科肿瘤
Serous ovarian cancer (SOC) is the most lethal gynecological cancer. Clinical studies have revealed an association between tumor stage and grade and clinical prognosis. Identification of meaningful clusters of co-expressed genes or representative biomarkers related to stage or grade may help to reveal mechanisms of tumorigenesis and cancer development, and aid in predicting SOC patient prognosis. We therefore performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on three public microarray datasets (GSE26193, GSE9891, and TCGA), which included 788 samples and 10402 genes. We detected four modules related to one or more clinical features significantly shared across all modeling datasets, and identified one stage-associated module and one grade-associated module. Our analysis showed that MMP2, COL3A1, COL1A2, FBN1, COL5A1, COL5A2, and AEBP1 are top hub genes related to stage, while CDK1, BUB1, BUB1B, BIRC5, AURKB, CENPA, and CDC20 are top hub genes related to grade. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggest that extracellular matrix interactions and mitotic signaling pathways are crucial determinants of tumor stage and grade. The relationships between gene expression modules and tumor stage or grade were validated in five independent datasets. These results could potentially be developed into a more objective scoring system to improve prediction of SOC outcomes.
基金:
National Basic Research Program of China (973 Program) [2015CB553903]; National Science-technology Support Plan [2015BAI13B05]; Nature and Science Foundation of China [81472783, 81630060, 81502258, 81272859, 30801340, 81230038, 81202061, 81402163, 81402164, 81472444, 81302266, 81572725, G30973184, WJ2015MA001]
第一作者单位:[1]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Cancer Biol Res Ctr,Key Lab,Minist Educ,Wuhan,Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Sun Qian,Zhao Haiyue,Zhang Cong,et al.Gene co-expression network reveals shared modules predictive of stage and grade in serous ovarian cancers[J].ONCOTARGET.2017,8(26):42983-42996.doi:10.18632/oncotarget.17785.
APA:
Sun, Qian,Zhao, Haiyue,Zhang, Cong,Hu, Ting,Wu, Jianli...&Zhu, Tao.(2017).Gene co-expression network reveals shared modules predictive of stage and grade in serous ovarian cancers.ONCOTARGET,8,(26)
MLA:
Sun, Qian,et al."Gene co-expression network reveals shared modules predictive of stage and grade in serous ovarian cancers".ONCOTARGET 8..26(2017):42983-42996