CAV1 和 CAV2 在头颈部鳞状细胞癌中的预后价值。
Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma.
机构信息
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
出版信息
Biomolecules. 2023 Feb 6;13(2):303. doi: 10.3390/biom13020303.
BACKGROUND
The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue.
METHODS
We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results.
RESULTS
Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC ( < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, = 0.027; CAV2: HR: 1.408, = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion ( < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 ( < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC ( < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes ( < 0.05).
CONCLUSIONS
The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.
背景
CAV 家族，尤其是 CAV1 和 CAV2，与肿瘤的发生发展显著相关。本研究通过生物信息学分析并在人体组织中验证，旨在探讨 CAV1 和 CAV2 在头颈部鳞状细胞癌（HNSCC）中的致病和预后作用。
方法
我们通过癌症基因组图谱中的数据，分析了 CAV1 和 CAV2 在 HNSCC 及正常组织中的表达谱。通过 Xena 浏览器获取 Kaplan-Meier 生存曲线，并进行 Cox 回归分析，以检验预后意义。将共表达基因上传至 GeneMANIA，并进行基因本体论和京都基因与基因组百科全书分析，以展示相互作用网络。通过基因集富集分析分析 CAV1 和 CAV2 在 HNSCC 中的信号通路，以阐明潜在的调控机制。通过比较毒理学基因组数据库探索基因-药物相互作用网络。通过免疫组织化学验证理论结果。
结果
与正常组织相比，CAV1 和 CAV2 在 HNSCC 中的表达水平显著升高（<0.0001），这独立提示 OS 不良（CAV1：HR：1.146，=0.027；CAV2：HR：1.408，=0.002）。通过 FunRich 与 CAV1 和 CAV2 分析共表达基因（PXN、ITGA3、TES 和 MET），发现与粘着斑（<0.001）显著相关，这对癌症的进展有重要影响。GSEA 还显示细胞蛋白分解代谢过程（ES=0.42）和蛋白酶体复合物（ES=0.72），这是参与氧化损伤和细胞周期及转录的蛋白质的关键降解系统，与 CAV2 在 HNSCC 中的高表达密切相关。更重要的是，我们发现了 HNSCC 免疫微环境中不同免疫细胞浸润程度与 CAV1/CAV2 表达水平之间的关系（<0.0001）。通过 CTD 检查基因-药物相互作用网络。此外，组织微阵列验证了 CAV1/CAV2 在 HNSCC 中的高表达（<0.0001），高表达亚组提示临床结局显著较差（<0.05）。
结论
研究结果表明，CAV1 和 CAV2 在 HNSCC 中通常上调，可能预测预后不良。
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