Peng Guo, Dan Wang, Jun Wu, Junjun Yang, Tong Ren, Baoli Zhu, Yang Xiang
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, No. 1 Shuai Fu Yuan, Wang Fu Jing Street, Beijing, 100730, People's Republic of China.
Tumour Biol. 2015 May;36(5):3309-17. doi: 10.1007/s13277-014-2963-0. Epub 2015 Jan 14.
Cervical cancer is the third most common cancer and the fourth leading cause of cancer deaths among women in the world. The discovery of vital diagnostic and therapeutic markers against cervical squamous cell carcinoma (CSCC) would broaden our understanding on the molecular basis of CSCC. In this study, we thoroughly analyzed the transcriptome of CSCC and matched adjacent nontumor (ATN) tissue. RNA sequencing was performed to screen the differentially expressed genes (DEGs) of three pairs of CSCC and ATN tissues. Functional enrichment analysis was used to uncover the biological functions of DEGs. Protein interaction network was carried out to reveal interaction of DEGs. Quantitative real-time PCR was conducted to validate the expression of DEGs. Immunohistochemistry was used to detect the relationship between clinicopathological parameters of CSCC and DEGs. There were a total of 347 significantly common DEGs in the three paired examples, including 104 consistent upregulated and 148 consistent downregulated DEGs. The 347 DEGs were categorized into 73 functional categories by Gene Ontology (GO) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested six significantly signal pathways. The protein interaction network uncovered three important DEGs, including retinol dehydrogenase 12 (RDH12), ubiquitin D (UBD), and serum amyloid A1 (SAA1). We found that RDH12 expression was decreased in 74.5 % of CSCC tissues. RDH12 expression was negatively associated with tumor size and depth of cervical invasion. The UBD was overexpressed in 61.7 % of CSCC tissues and was positively related with tumor size and lymphatic metastasis. The SAA1 protein was overexpressed in 57.4 % of CSCC tissues and was positively related with clinicopathological parameters of tumor size, lymphatic metastasis, and depth of cervical invasion. The RDH12, UBD, and SAA1 genes might participate in the progression of CSCC.
宫颈癌是全球女性中第三大常见癌症，也是癌症死亡的第四大主要原因。发现针对宫颈鳞状细胞癌（CSCC）的重要诊断和治疗标志物将拓宽我们对CSCC分子基础的理解。在本研究中，我们全面分析了CSCC及其配对的相邻非肿瘤（ATN）组织的转录组。进行RNA测序以筛选三对CSCC和ATN组织中的差异表达基因（DEG）。功能富集分析用于揭示DEG的生物学功能。构建蛋白质相互作用网络以揭示DEG之间的相互作用。进行定量实时PCR以验证DEG的表达。免疫组织化学用于检测CSCC临床病理参数与DEG之间的关系。在三对样本中共有347个显著共有的DEG，包括104个一致上调和148个一致下调的DEG。通过基因本体论（GO）分析，这347个DEG被分类为73个功能类别。京都基因与基因组百科全书（KEGG）通路富集分析表明有六个显著的信号通路。蛋白质相互作用网络揭示了三个重要的DEG，包括视黄醇脱氢酶12（RDH12）、泛素D（UBD）和血清淀粉样蛋白A1（SAA1）。我们发现74.5%的CSCC组织中RDH12表达降低。RDH12表达与肿瘤大小和宫颈浸润深度呈负相关。61.7%的CSCC组织中UBD过表达，且与肿瘤大小和淋巴转移呈正相关。57.4%的CSCC组织中SAA1蛋白过表达，且与肿瘤大小、淋巴转移和宫颈浸润深度的临床病理参数呈正相关。RDH12、UBD和SAA1基因可能参与CSCC的进展。
