Association Study Of CSMD1Gene And BRG1Gene With Oncogenesis Of Laryngeal Squamous Cell Carcinoma

Head and neck cancer is the sixth largest common human tumor types, accounting for5%of the total body malignant tumor^[1].Survey figures showed that global with650000newcases each year in patients with head and neck cancer[2]. Laryngeal cancer in the head andneck in malignant tumor the largest^[3],95%-98%of the pathological types of squamous cellcarcinoma[4].Throat squamous cell carcinoma is derived from the throat epithelium of theorganization’s malignant tumor[5]. The disease onset to45-75years old men are in themajority. Three types of laryngeal cancer, the most frequent in the subglottic type, second inthe subglottic type, subglottic type at least[6]. The tumor tissue parting stages and lymphnode metastasis[7]judgment is recurrent and important diagnostic index of poor prognosis.Human chromosome8p23.2often happen LOH phenomenon, become Head and NeckSquamous Cell Carcinoma （Head and Neck Squamous Cell Carcinoma HNSCC） a hot issue.Presumably the area there is a tumor suppressor genes （tumor suppressor gene, TSG）.CSMD1（CUB and Sushi multiple domain1） gene location in chromosome8p23.2,encoded protein membrane might be involved in membrane material exchange and signaltransduction, can be in breast cancer and prostate cancer and stomach cancer, the expressionin the tumor. According to the position of the genome, expression patterns and proteinhomology, speculation CSMD1head and neck squamous cell carcinoma is one of theimportant tumor-suppressor genes. But because CSMD1genome sequencing large Numbers,and CSMD1protein function of little is known, and research progress of limited, so far, toCSMD1deactivation mechanism in the laryngeal cancer remains to be seen. Depletion（brahma-related gene1） is human SWI/SNF chromatin remodeling the core of the compoundenzyme, belong to a nuclear transcription factors, in the protein-proteins play activationfunction transcription role. ATP needed for cell growth kinetic energy, transcription factors inmolecules containing a depletion of the enzyme combined with DNA rely on ATPase area,the cell growth related proteins on negative regulatory role. In the first study, depletion in thestudy of genetic mutations HNSCC primary stage limited to, not definite mechanism.Depletion in the expression in the throat was thought to lack of laryngeal cancer occurrenceand development of related^[59]. This study based on this, the preliminary discussion in signal transduction pathways in depletion of the regulation of gene CSMD1role, this researchreport has not been seen.In recent years, China’s overall trend of type of throat cancer-the rise, in the northeastwas particularly outstanding. And in jilin area in northeast China has typical of thegeographical environment characteristics. This research collected35patients in jilin areaHNSCC han people organization and the cancer patients laryngeal cancer tissue samples, inCSMD1microsatellite loci internal selection D8S262, D8S518, D8S1781, D8S1788anddepletion microsatellite loci selection near D19S581, D19S584, the above six geneticmarkers lock on chromosome8p23.2and19p13.2, through the polymerase chainreaction-Single, Conformation Polymorphism （polymerase chain reaction-Single StrandConformation Polymorphism, PCR-SSCP） technology, according to the specificmicrosatellite marker heterozygosity missing （loss of heterozygosity, LOH） specific alleleheterozygosity of missing area, and through the immunohistochemical （immunohist-ochemistry） dyeing inspection of tumor suppressor genes expression level. Statisticalanalysis alleles depletion and CSMD1heterozygosity lack the incidence and CSMD1positive expression rate in jilin area laryngeal cancer with age, sex, patient TNM staging,pathology classification and lymph node metastasis factors connection.Results show that the PCR-SSCP, six sites all appear microsatellite instability（microsatellite instability, MSI）, which D8S518site microsatellite instability had the highestfrequency, to45.8%, in addition to D8S1781outside, the rest of the site also appear theheterozygosity flaw, microsatellite loci happened D19S581sites heterozygosity loss of47.8%. CSMD1internal D8S262, D8S518, D8S1781, D8S1788four microsatellite（microsatellite, MS） site, span less than2.5Cm, all appear MSI, the highest frequency MSIhappened D8S518sites reached45.8%, higher than other microsatellite loci, and the totalmutation rate was62.5%. In addition to D8S1781outside, three other sites all appear LOH,the highest frequency of16.7%. One example in three sites occurs at least a LOH or MSIchange, there are4cases in two sites also happened at least one LOH and MSI change.Explain the tumor suppressor genes CSMD1MSI and LOH of frequent, in the northeast oflaryngeal cancer in people have a higher mutation rate.19p on chromosome lack of frequent,and laryngeal cancer clinical TNM stage, and presence of lymph node metastasis weresignificantly related to （p <0.05）, presumably the area and tumor invasion and metastasis areclosely related. Suggests the site area near the existence of a related with laryngeal cancertumor suppressor genes, depletion heterozygosity loss as early diagnosis of poor prognosis a reference index. CSMD1in the cell membrane positive expression, Immunohistochemicalresults show that the nuclear appears deep purple, in the laryngeal cancer pathologicalorganization, CSMD1is uniformity positive expresstion in the extracellular matrix,which is tan-yellow dyeing, and membrane is complete. In the cancer organization, the cellsarround were covered with positive,or there are strain protein beside nucleus. dyeing is notuniform, tan more, parts of areas of the cell membrane are lack.In contrast, the cancer groupof positive10/10is more than laryngeal cancer group of positive14/21. Both groups havesignificant difference in statistics（P <0.05）, CSMD1positive expression rate and laryngealcancer patients of gender, age, TNM staging, pathology classification is not related factors（P>0.05）, with only a lymph node metastasis related （P <0.05）. Tip laryngeal cancer in theexpression of the organization CSMD1weakened and tumor of the lymph node metastasisthere is a close relationship, immunohistochemical results and PCR-SSCP results reflect thelack of common CSMD1expression and tumor invasion and metastasis relevant. In thethroat, CSMD1expression is reduced and depletion lose is proportional to the expression.Conclusion: depletion and CSMD1are for laryngeal cancer suppressor genes, CSMD1rapiddivision of the normal epithelial cells with adsorption effect, by invading basementmembrane in the descent of the tumor with transfer; By the experimental result speculation,transcription factors in cell signaling may depletion in the regulation of tumor suppressorgenes CSMD1transcription role.Microsatellite heterozygosity hiatus phenomenon in the genome of the tumor generallyoccur, and cells in the process of malignant change often with tumor suppressor genes lackof high frequency, cause people high attention. The satellite is a kind of good geneticmarkers, medical use microsatellite LOH in all the genome candidate in high position oftumor suppressor genes, but most of the satellite is located in the area of the gene encoding,immunohistochemical techniques more direct reaction tumor suppressor gene expression inthe level of change. Use a combination of microsatellite genetic markers andimmunohistochemical tumor marker of throat squamous cell carcinoma high-risk groups andprognosis for early evaluation, thereby preventing the occurrence of laryngeal cancer andguide clinical treatment.