CSTA 表达降低促进口腔鳞状细胞癌的淋巴转移并预测不良预后。
Decreased CSTA expression promotes lymphatic metastasis and predicts poor survival in oral squamous cell carcinoma.
机构信息
Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, China; National Center for Stomatology, Shanghai, 200011, China; National Clinical Research Center for Oral Diseases, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.
Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, China; National Center for Stomatology, Shanghai, 200011, China; National Clinical Research Center for Oral Diseases, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China; School of Stomatology, Weifang Medical University, Weifang, 261031, Shandong, China.
出版信息
Arch Oral Biol. 2021 Jun;126:105116. doi: 10.1016/j.archoralbio.2021.105116. Epub 2021 Mar 31.
OBJECTIVE
Herein, we aimed to identify biomarkers that affect lymphatic metastasis of oral squamous cell carcinoma (OSCC) through bioinformatic analysis, and clinicopathological and in vitro verifications.
DESIGN
The OSCC-related gene expression dataset was retrieved from The Cancer Genome Atlas (TCGA) and analyzed to identify differentially expressed genes (DEGs), which were subjected to pathway analysis. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed to identify hub genes. Expression of potential biomarkers was examined using quantitative real-time polymerase chain reaction, immunohistochemistry, and western blotting. Statistical analyses were performed to determine the association between biomarker expression and clinicopathological characteristics of patients with OSCC. Effects of selected biomarkers on proliferation, migration, and invasion were evaluated using in vitro assays.
RESULTS
For DEGs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed potential lymphatic metastasis-related biological processes and signaling pathways. Eight hub genes - ALOXE3, CSTA, PLA2G4E, PPL, SPRR1A, SPRR2A, SPRR2D, and SPRR2E, were identified via WGCNA and PPI analyses. CSTA expression was markedly downregulated in primary OSCC tissues, and low CSTA expression significantly correlated with high tumor grade (P = 0.001), nodal metastasis (P = 0.028), and poor overall survival (P < 0.001). CTSA overexpression inhibited OSCC cell migration and invasion in vitro, with little effect on OSCC cell proliferation.
CONCLUSIONS
Our study revealed that CSTA is a promising biomarker and therapeutic target with prognostic implications in patients with OSCC. CSTA may play an essential role in OSCC lymphatic metastasis and tumor differentiation.
目的
通过生物信息学分析，并结合临床病理和体外验证，旨在确定影响口腔鳞状细胞癌（OSCC）淋巴转移的生物标志物。
设计
从癌症基因组图谱（TCGA）中检索与 OSCC 相关的基因表达数据集，以鉴定差异表达基因（DEGs），并对其进行通路分析。采用加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络分析鉴定关键基因。采用定量实时聚合酶链反应、免疫组织化学和蛋白质印迹法检测潜在生物标志物的表达。采用统计学分析确定 OSCC 患者生物标志物表达与临床病理特征的相关性。采用体外实验评估选定生物标志物对增殖、迁移和侵袭的影响。
结果
对于 DEGs，基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析揭示了潜在的与淋巴转移相关的生物学过程和信号通路。通过 WGCNA 和 PPI 分析鉴定了 8 个关键基因——ALOXE3、CSTA、PLA2G4E、PPL、SPRR1A、SPRR2A、SPRR2D 和 SPRR2E。CSTA 在原发性 OSCC 组织中的表达明显下调，低 CSTA 表达与高肿瘤分级（P=0.001）、淋巴结转移（P=0.028）和总体生存不良（P<0.001）显著相关。CTSA 过表达显著抑制 OSCC 细胞的迁移和侵袭，对 OSCC 细胞的增殖影响较小。
结论
本研究表明，CSTA 是一种有前途的生物标志物和治疗靶点，对 OSCC 患者具有预后意义。CSTA 可能在 OSCC 淋巴转移和肿瘤分化中发挥重要作用。
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