南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (12): 2111-2117.doi: 10.12122/j.issn.1673-4254.2023.12.16

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IL-34在舌鳞状细胞癌中的表达及意义

张伟健，邹琸玥，朱永娜，王 敏，马彩云，武峻捷，石 昕，刘 茜   

  1. 蚌埠医学院第二附属医院口腔科，安徽 蚌埠 233040；蚌埠医学院口腔医学院，感染与免疫安徽省重点实验室，生命科学学院，安徽 蚌埠 233030
  • 出版日期:2023-12-20 发布日期:2023-12-29

Expression of interleukin-34 in tongue squamous cell carcinoma and its clinical implications

ZHANG Weijian, ZOU Zhuoyue, ZHU Yongna, WANG Min, MA Caiyun, WU Junjie, SHI Xin, LIU Xi   

  1. Department of Stomatology, Second Affiliated Hospital ,Bengbu Medical College, Bengbu 233040, China; Department of stomatology, Bengbu Medical College, Anhui Province Key Laboratory of Infection and Immunity, School of Life Sciences, Bengbu Medical College, Bengbu 233030, China
  • Online:2023-12-20 Published:2023-12-29

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摘要： 目的 探讨白细胞介素34（IL-34）在舌鳞状细胞癌（TSCC）中的表达及临床病理学意义。方法 使用酶联免疫吸附法（ELISA）检测IL-34在36例TSCC患者和36例正常人群血清中表达水平；通过免疫组织化学（IHC）以及实时荧光定量PCR技术（qRT-PCR）比较41例TSCC患者癌组织和癌旁组织中 IL-34 的表达情况，并进一步分析其表达情况与TSCC患者临床病理特征之间的关系；利用 String数据库，LinkedOmics数据库和GEO数据库获得在TSCC中IL-34相关差异基因，通过Webgestalt数据库对TSCC中IL-34相关基因进行基因本体论（GO）功能分析和京都基因与基因组百科全书（KEGG）信号通路富集分析。结果 ELISA结果显示TSCC患者血清IL-34浓度低于正常人群，差异有统计学意义（P<0.001）；IHC和qRT-PCR结果显示与TSCC患者癌组织相比，IL-34在TSCC患者癌旁组织中高表达，差异有统计学意义（P<0.001），在癌组织中IL-34的表达水平和淋巴结是否转移，TNM分期有关（P<0.05），而与TSCC患者的年龄、性别、是否吸烟、是否喝酒以及肿瘤大小无关（P>0.05）；通过数据库分析发现IL-34与CSF1R，PTPRJ相关性最强，GO功能分析结果显示：在TSCC中IL-34及相关基因在生物学过程（BP）中，主要富集在骨髓细胞分化等；在细胞组成(CC)中，主要富集在含胶原蛋白的细胞外基质等；在分子功能（MF）中，主要富集在细胞因子结合、信号受体激活剂活性等。KEGG信号通路富集显示：IL-34及相关差异基因主要参与破骨细胞分化，癌症中的蛋白多糖，MAPK信号通路等。结论 IL-34在TSCC中低表达且参与TSCC的发生、发展，有望成为TSCC新的诊断标志物和治疗靶点。

关键词: 舌鳞状细胞癌；白细胞介素34；肿瘤微环境；生物信息学

Abstract: Objective To investigate the expression of interleukin-34 (IL-34) in tongue squamous cell carcinoma (TSCC) and its clinical implications. Methods Serum IL-34 level was detected in 36 patients with TSCC and 36 healthy individuals using enzyme-linked immunosorbent assay (ELISA). The expressions of IL-34 mRNA and protein levels in TSCC and adjacent tissues were examined in 41 patients using real- time fluorescence quantitative PCR (qRT-PCR) and immunohistochemistry (IHC), and their correlation with the clinicopathological features of the patients was further analyzed. Informatic analysis of the differentially expressed genes related with IL-34 in TSCC was carried out based on String database, LinkedOmics database and GEO database, and GO functional analysis and KEGG signaling pathway enrichment analysis were performed using Webgestalt database. Results The serum level of IL-34 was significantly lower in TSCC patients than in the healthy individuals (P<0.001), and its expression level was also significantly lower in the tumor tissues than in the adjacent tissues (P<0.001). The expression level of IL-34 in TSCC tissues was related with lymph node metastasis and TNM staging (P<0.05), but not with age, gender, smoking, drinking, or tumor size (P>0.05). Informatic analysis suggested that IL-34 had the strongest correlation with CSF1R and PTPRJ. IL-34 and its related genes in TSCC were enriched mainly in bone marrow cell differentiation, collagen-containing extracellular matrix, and cytokine binding and signal receptor activator activity. KEGG signaling pathway enrichment showed that IL-34 and the related differentially expressed genes were involved mainly in osteoclast differentiation, protein polysaccharide in cancer, and the MAPK signaling pathway. Conclusion IL-34 is lowly expressed in TSCC and participates in the occurrence and progression of TSCC, and can be potentially used as a new diagnostic biomarker and therapeutic target for TSCC.

Key words: tongue squamous cell carcinoma; interleukin-34; tumor microenvironment; bioinformatics