| BackgroundOral squamous cell carcinoma(OSCC)is one of the most common malignant tumors of the head and neck,and the most common pathological type of oral malignant tumor,accounting for approximately 90%of oral cancers.The incidence of oral squamous cell carcinoma is still rising year by year and tends to be younger.According to statistics,about one-third of oral squamous cell carcinoma patients will eventually develop life threatening and incurable recurrent oral squamous cell carcinoma.In the past 30 years,the overall 5-year survival rate of oral squamous cell carcinoma has been<50%,which is related to the characteristics of oral squamous cell carcinoma that are easy to metastasize and relapse.Oral squamous cell carcinoma is prone to deep infiltration and cervical lymph node metastasis due to the anatomical characteristics of the tongue and gums and the abundant lymphatic vessels containing a large number of anastomotic branches in the oral cavity.However,the molecular mechanism of OSCC cell invasion and metastasis is currently unclear.At present,the treatment of oral squamous cell carcinoma is still based on surgery,supplemented by radiotherapy and chemotherapy depending on the disease condition.However,due to the large surgical trauma,the decline in quality of life and the postoperative recurrence,most patients with oral squamous cell carcinoma have a poor prognosis.Therefore,there is an urgent need to find new ways of diagnosis and treatment for patients with oral squamous cell carcinoma.The current research on cancer tissues shows that there is a link between changes at the molecular level and the tissue level,and may play a key role in driving malignant changes in tissues and disease progression.Finding and studying the biomolecules related to the invasion and metastasis mechanism of oral squamous cell carcinoma can provide valuable data for the prevention and treatment of oral squamous cell carcinoma which can help to improve the low prognosis of patients with oral squamous cell carcinoma.Type Ⅳ collagen is a protein that is abundant and widely distributed in the human body,and is the main component of the basement membrane in the extracellular matrix.It is known that type Ⅳ collagen is composed of 6 α chains(α1～α6)coded by COL4A1～COL4A6 genes.These 6 α chains are connected in pairs to form the heterotrimeric structure of type Ⅳ collagen.Type Ⅳcollagen forms the skeleton of the cell basement membrane and provides a scaffold for cell growth.It can also recognize each other with specific receptors on the cell surface,participate in intracellular signal transduction pathways,and participate in biological processes such as cell adhesion,differentiation,and migration.Additionally,type Ⅳ collagen also plays a role in malignant biological processes such as tumor cell proliferation,invasion,and metastasis.The biological properties of type Ⅳ collagen make it closely related to the pathophysiological process of diseases and showing its research potential as a biomarker in tumor prevention and treatment.We obtained the differentially expressed genes of oral squamous cell carcinoma samples through public databases,and performed the enrichment analysis of the KEGG pathway for these genes.Through enrichment analysis,it is found that COL4A1,COL4A2 and COL4A6 genes are abundant in KEGG pathways associated with tumor invasion and metastasis,and are highly expressed in oral squamous cell carcinoma.Therefore,we selected these three genes as research genes to explore their correlation with oral squamous cell carcinoma,in order to raise the diagnosis and treatment level of oral squamous cell carcinoma,improve the prognosis of OSCC patients.Objective:Explore the expression levels of COL4A1,COL4A2,and COL4A6 proteins in oral squamous cell carcinoma tissues and non-cancerous tissues.To explores the differences and correlations of COL4A1,COL4A2 and COL4A6 protein expression levels in OSCC tissues,as well as their possible roles and molecular mechanisms in OSCCMethods:1.Immunohistochemistry experiment of 38 pairs oral squamous cell carcinoma and carcinogenic samples were used to verify the protein expression of COL4A1,COL4A2 and COL4A6 in oral squamous cell carcinoma and carcinogenic side samples,as well as the relationship with the corresponding clinical parameters.And to evaluate the differences in protein expression levels and connections between these three genes in oral squamous cell carcinoma tissues.2.Use public database data to screen out genes that are commonly related to COL4A1,COL4A2,COL4A6 and are differentially expressed in oral squamous cell carcinoma.GO annotation,KEGG enrichment analysis,PPI analysis of these OSCC differentially expressed genes related to COL4A1,COL4A2,and COL4A6 were performed to help explore the role of COL4A1,COL4A2,and COL4A6 genes in the occurrence and development of oral squamous cell carcinoma.Possible molecular mechanism.Result:1.Through the analysis of the results of immunohistochemistry,the protein expression level of COL4A,COL4A2,COL4A6 genes in oral squamous cell carcinoma was higher than that of non-cancerous tissue.COL4A2 and COL4A6 protein expression levels of oral squamous cell carcinoma tissue with lymph node metastasis were higher than without lymph node metastasis.To compare and analyze the protein expression levels of COL4A1,COL4A2,COL4A6 in oral squamous cell carcinoma tissues,we found that the protein expression level of COL4A6 in oral squamous cell carcinoma is higher than that of COL4A1 and COL4A2,and the protein expression of COL4A2 It is positively correlated with the expression of COL4A6.2.GO annotations were performed on genes that are commonly related to COL4A1,COL4A2,and COL4A6 that are differentially expressed in oral squamous cell carcinoma.The results suggest that these genes are mainly enriched in cell components and biological activities related to the extracellular matrix.The results of KEGG enrichment analysis indicated that the OSCC differentially expressed genes related to COL4A1,COL4A2,and COL4A6 are in the four cell signaling pathways related to the occurrence and development of tumors:Human papillomavirus infection,ECM-receptor interaction,Focal adhesion and PI3K-Akt Significantly enriched.The hub genes of PPI network have also been found to be related to the occurrence and development of tumors in a number of studies.Conclusion:1.COL4A1,COL4A2,and COL4A6 gene encoding proteins are up-regulated in oral squamous cell carcinoma,and the level of COL4A2 and COL4A6 protein expression is associated with lymph node metastasis in patients with oral squamous cell carcinoma.The protein expression level of COL4A6 is higher than that of COL4A1 and COL4A2.Since COL4A1 and COL4A2 coded proteins together constitute the most common heterotrimeric form of type Ⅳcollagen and there is a positive correlation between the protein expression levels of COL4A6 and COL4A2,the protein expression of these three genes are related.The up-regulation of COL4A1,COL4A2 and COL4A6 may affect the occurrence and development of OSCC together.2.COL4A1,COL4A2,COL4A6 genes and their encoded proteins have an interaction relationship with genes and proteins of other related components of the extracellular matrix.And COL4A1,COL4A2,COL4A6 may affect the occurrence and development of OSCC through the Human papillomavirus infection pathway,ECM-receptor interaction pathway,Focal adhesion pathway,PI3K-Akt pathway and protein interactions. |
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