Decreased CSTA expression promotes lymphatic metastasis and predicts poor survival in oral squamous cell carcinoma. (June 2021)

• Record Type: Journal Article
• Authors: Wang, Yupu; Wang, Lin; Li, Xing; Qu, Xingzhou; Han, Nannan; Ruan, Min; Zhang, Chenping
• Is Part Of: Archives of oral biology. Volume 126(2021)
• Publication Date: 2021-06
• Subjects: ALOXE3 arachidonate lipoxygenase 3 -- ANT adjacent non-tumor tissue -- CSTA cystatin A -- CSTB cystatin B -- DEG differentially expressed gene -- EMT epithelial-mesenchymal transition -- VPL envoplakin -- GnRH gonadotrophin-releasing hormone -- GO gene ontology -- GRHL3 grainyhead like transcription factor 3 -- HNSCC head and neck squamous cell carcinoma -- HPV human papillomaviruses -- IHC immunohistochemistry -- KEGG kyoto encyclopedia of genes and genomes -- KLK10 kallikrein related peptidase 10 -- LN lymph node -- LVI lymphovascular invasion -- OS overall survival -- PGLYRP3 peptidoglycan recognition protein 3 -- PLA2G4E phospholipase A2 Group IV -- PPI protein-protein interaction -- PPL periplakin -- SPRR small proline rich protein -- STRING search tool for the retrieval of interacting genes/protein -- SULT2B1 sulfotransferase family 2B member 1 -- TCGA the cancer genome atlas -- TOM topological overlap matrix -- WGCNA weighted gene co-expression network analysis; Oral squamous cell carcinoma -- Lymphatic metastasis -- Biomarker -- Bioinformatics -- Cystatin A; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2021.105116
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: Eight lymphatic metastasis-related hub genes were identified in OSCC. CSTA expression significantly correlated with tumor grade, nodal metastasis, and OS. Gain of cystatin A ( CSTA ) could suppress OSCC cell migration and invasion in vitro . Potential mechanisms for OSCC lymphatic metastasis were analyzed and discussed. Abstract: 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.