Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical squamous cell carcinoma patients by RNA sequencing
Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical squamous cell carcinoma patients by RNA sequencing
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通过 RNA 测序对宫颈鳞状细胞癌患者的癌症和邻近非肿瘤组织进行转录组分析。
DOI：
10.1007/s13277-014-2963-0
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发表时间：
2015-05-01
期刊：
影响因子：
--
通讯作者：
Yang, Xiang
中科院分区：
文献类型：
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作者：
Peng, Guo;Dan, Wang;Yang, Xiang
子宫颈癌是世界上第三大最常见的癌症，也是导致妇女癌症死亡的第四大原因。宫颈鳞状细胞癌（CSCC）重要诊断和治疗标志物的发现将拓宽我们对CSCC分子基础的认识。在这项研究中，我们彻底分析了CSCC和匹配的相邻非肿瘤（ATN）组织的转录组。通过RNA测序技术筛选3对CSCC和ATN组织的差异表达基因（DEG）。功能富集分析用于揭示DEG的生物学功能。蛋白质相互作用网络揭示DEG的相互作用。进行定量实时PCR以验证DEG的表达。采用免疫组化方法检测癌组织中DEG与临床病理参数的关系。在三个配对的例子中，总共有347个显著常见的DEG，包括104个一致上调的DEG和148个一致下调的DEG。通过基因本体（GO）分析将347个DEG分为73个功能类别。京都基因和基因组百科全书（KEGG）途径富集分析提出了6条重要的信号途径。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（RDH 12），泛素D（UBD）和血清淀粉样蛋白A1（SAA 1）。我们发现RDH12在74.5%的CSCC组织中表达降低。RDH12表达与肿瘤大小和宫颈浸润深度呈负相关。UBD在61.7%的CSCC组织中过表达，且与肿瘤大小、淋巴结转移呈正相关。SAA 1蛋白在57.4%的CSCC组织中过表达，且与肿瘤大小、淋巴结转移和宫颈浸润深度等临床病理参数呈正相关。RDH12、UBD和SAA 1基因可能参与了CSCC的发生发展。
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.