Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma

Jingyu He; Simin Ouyang; Yilong Zhao; Yuqi Liu; Yaolong Liu; Bing Zhou; Qiwen Man; Bing Liu; Tianfu Wu

doi:10.3390/biom13020303

Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma

Biomolecules. 2023 Feb 6;13(2):303. doi: 10.3390/biom13020303.

Authors

Jingyu He^{1

2}, Simin Ouyang¹, Yilong Zhao¹, Yuqi Liu¹, Yaolong Liu¹, Bing Zhou², Qiwen Man^{1

2}, Bing Liu^{1

2}, Tianfu Wu^{1

2}

Affiliations

¹ Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
² 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.

Abstract

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 (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 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 (p < 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 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05).

Conclusions: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.

Keywords: CAV1; CAV2; bioinformatic analysis; biomarker; head and neck squamous cell cancer; immune infiltration; immunohistochemistry; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Computational Biology*
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms* / genetics
Humans
Kaplan-Meier Estimate
Prognosis
Squamous Cell Carcinoma of Head and Neck / genetics
Tumor Microenvironment

Substances

Biomarkers, Tumor

Grants and funding

This study was supported by grants from the Health Commission of Hubei Province scientific research project (NO. WJ2021M179 to Tianfu Wu and NO. WJ2021M175 to Bing Liu) and the National Natural Science Foundation of China (grant NO. 82001066 to Qiwen Man).