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Deciphering the genetic alterations in matrix metallo-proteinase gene family and its putative association with head and neck squamous cell carcinoma.

ABSTRACT: Matrix metallo-proteinases (MMPs) a group of zinc-dependent proteolytic enzymes which play a key role in tumorigenesis by degrading almost all extracellular matrix (ECM) components. MMPs are associated with tumour progression including invasion, angiogenesis, metastasis and poor prognosis. Genetic alterations such as single nucleotide variations and other gross chromosomal abnormalities have been found to drive the process of malignant transformation. In line with the above facts, the present study aims to analyse the genetic alterations, associated gene expression patterns and survival probability of HNSCC patients upon differential expression of the crucial members of the MMP family. The observational study utilised several computational tools. The cBioportal database was used as the primary source of identification of genetic alterations in the MMP family of genes. The Cancer Gene Atlas dataset (Firehose Legacy) was used for the investigations. The highest frequency of alteration was identified in the MMP20 gene (8%). The common gene alterations were amplifications, deep deletions, mis-sense and truncating mutations. Interestingly, amplification and deep deletion followed the same pattern in about 31 patients, in genes MMP1, 3, 7, 8, 10, 12, 20, and 27. The MMP20 gene expression analysis showed a significant difference between the normal subjects and the patients with primary tumors (6.95 x 10^-4). The Kaplan-Meier survival curve analysis identified that female patients with high-level expression of the MMP20 gene had a low survival probability when compared to male HNSC patients. Taken together, the present study provides preliminary information about the involvement of the MMP20 gene of the MMP family with HNSCC. Further experimental analysis is required to derive a strong association between the gene alterations observed with HNSCC.

SUBMITTER: Aparna J

PROVIDER: S-EPMC7936386 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Deciphering the genetic alterations in matrix metallo-proteinase gene family and its putative association with head and neck squamous cell carcinoma.

Aparna Jambukeswaran J Smiline-Girija Aseervatham Selvi AS Paramasivam Arumugam A Vijayashree-Priyadharsini Jayaseelan J

Molecular biology research communications 20210301 1

Matrix metallo-proteinases (MMPs) a group of zinc-dependent proteolytic enzymes which play a key role in tumorigenesis by degrading almost all extracellular matrix (ECM) components. MMPs are associated with tumour progression including invasion, angiogenesis, metastasis and poor prognosis. Genetic alterations such as single nucleotide variations and other gross chromosomal abnormalities have been found to drive the process of malignant transformation. In line with the above facts, the present st ...[more]

PMID: 33681393

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Project description:Head and neck squamous cell carcinoma (HNSCC) arises from the epithelial lining of the oral cavity, hypopharynx, oropharynx, and larynx. There are several potential risk factors that cause the generation of HNSCC, including cigarette smoking, alcohol consumption, betel quid chewing, inadequate nutrition, poor oral hygiene, HPV and Epstein-Barr virus, and Candida albicans infections. HNSCC has causative links to both environmental factors and genetic mutations, with the latter playing a more critical role in cancer progression. These molecular changes to epithelial cells include the inactivation of cancer suppressor genes and proto-oncogenes overexpression, resulting in tumour cell proliferation and distant metastasis. HNSCC patients have impaired dendritic cell (DC) and natural killer (NK) cell functions, increased production of higher immune-suppressive molecules, loss of regulatory T cells and co-stimulatory molecules and major histocompatibility complex (MHC) class Ι molecules, lower number of lymphocyte subsets, and a poor response to antigen-presenting cells. At present, the standard treatment modalities for HNSCC patients include surgery, chemotherapy and radiotherapy, and combinatorial therapy. Despite advances in the development of novel treatment modalities over the last few decades, survival rates of HNSCC patients have not increased. To establish effective immunotherapies, a greater understanding of interactions between the immune system and HNSCC is required, and there is a particular need to develop novel therapeutic options. A therapeutic cancer vaccine has been proposed as a promising method to improve outcome by inducing a powerful adaptive immune response that leads to cancer cell elimination. Compared with other vaccines, peptide cancer vaccines are more robust and specific. In the past few years, there have been remarkable achievements in peptide-based vaccines for HNSCC patients. Here, we summarize the latest molecular alterations in HNSCC, explore the immune response to HNSCC, and discuss the latest developments in peptide-based cancer vaccine strategies. This review highlights areas for valuable future research focusing on peptide-based cancer vaccines.

Dataset Information

Deciphering the genetic alterations in matrix metallo-proteinase gene family and its putative association with head and neck squamous cell carcinoma.

Publications

Deciphering the genetic alterations in matrix metallo-proteinase gene family and its putative association with head and neck squamous cell carcinoma.

Similar Datasets

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