Yang Xi, Wu Kailiu, Li Siyi, Hu Longwei, Han Jing, Zhu Dongwang, Tian Xuerui, Liu Wei, Tian Zhen, Zhong Laiping, Yan Ming, Zhang Chenping, Zhang Zhiyuan
Department of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Department of Oral Pathology, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Oncotarget. 2017 Jan 10;8(2):2525-2535. doi: 10.18632/oncotarget.12446.
The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.
本研究的目的是通过大规模基因表达谱分析，确定可预测早期舌鳞状细胞癌（TSCC）及其隐匿性颈淋巴结转移预后的候选基因。从TSCC患者中收集肿瘤组织和配对的正常黏膜样本，并用Affymetrix HTA2.0高密度寡核苷酸阵列进行分析。对伴有颈淋巴结转移（CLNM）的TSCC中差异表达的基因，进一步用基因本体论和京都基因与基因组百科全书分析其功能和相关途径。与无CLNM的TSCC样本（n = 6）相比，通过微阵列在有CLNM的TSCC样本（n = 6）中总共鉴定出107个差异表达基因（p < 0.05）。选择参与细胞-基质黏附连接和迁移功能的基因，包括MFAP5、TNNC1、MGP、FBFBP1和FBXO32，并在TSCC样本（n = 32）中通过RT-PCR进行验证。在这五个基因中，通过免疫组织化学（n = 61）进一步验证了MFAP5和TNCC1的表达。观察到MFAP5和TNNC1表达之间存在显著正相关（p<0.001）。值得注意的是，MFAP5和TNNC1的过表达与CLNM、转移无复发生存率和总生存率相关。我们的研究结果表明，MFAP5和TNNC1可能是预测口腔舌癌隐匿性颈淋巴结转移和预后的潜在标志物。
