Preliminary Screening Of Carcinogenesis-Related Gene In Lung Squamous Cell Carcinoma By SNP6.0 Gene Chip And Initiatory Study Of PTPN13 Gene In Invasion And Metastasis Of Lung Squamous Cell Carcinoma

Background and objective: Lung cancer is one of the most common malignantdiseases and its mortality is the highest in cancer. It is severely detrimental topeople’s health and life. The incidence of lung cancer has a marked ascend trendin our country, especially in the female living in the city. At the beginning ofthis century, the mortality of lung cancer has increased from the fourth in 1970sto the first place now. The most common histopathologic type of lung cancer issquamous cell carcinoma, which is not sensitive to treat with chemoradiationtherapy. Once the cancer developed clinical metastasis, the curative effect oftherapy is often very bad. Thus, it is very important to develop a new strategyfor early prophylaxis, early diagnosis, prognosis warning, and personalizedtherapy in lung cancer.Along with the rapid development of new polymorphic geneticmarkers–SNP, it’s getting possible for us in learning genome wide moleculargenetic information, including LOH (loss of heterozygosity) and CNV (copynumber variation). Based on the Genome-Wide Human SNP Array 6.0 from Affymetrix, we can easily screen the whole human genome molecular geneticsinformation. Generally, high frequent LOH in some region on a chromosomeoften indicates some tumor suppressor genes, and CNV also has been proved tobe related with tumor.In this study, SNP 6.0 gene chip was applied to analyses genome widemolecular genetics information and carcinogenesis-related genes andchromosome segments were preliminarily screened in 10 cases of lungsquamous cell carcinoma. In addition, some genes and chromosome segmentsrelated to invasion and metastasis of lung squamous cell carcinoma were studiedinitiatorily. This study provides a basis for further mechanisms study, as well asfor the development of a new strategy for prevention and therapy in lung cancer,which includes early prophylaxis, early diagnosis, prognosis warning, andpersonalized therapy.ThiThis study contains two parts:Part one:Preliminary screening of carcinogenesis-related gene in lung squamous cellcarcinoma by SNP 6.0 Gene ChipMethods：Lung squamous cell carcinoma tissues were dissected via lasercapture microdissection technology, and SNP 6.0 gene chip was appliedanalyses the genome wide LOH and CNV.Results：1、In CNV analysis, obvious proliferation of some genes and chromosomesegments were observed on chromosome 3, and high frequent deletion ofsome genes and chromosome segments were observed on chromosome 4.2、In cases with lymph nodes metastasis, the number of genes and chromosomesegments with high frequent LOH is much more than that in the cases without lymph nodes metastasis. In addition, high frequent LOH was observed onchromosome 4q in all of the 4 cases with lymph nodes metastasis, especially on4q18-32.MaiMain Conclusions：Some new genes and chromosome segments onchromosome 4q may related with the development of lung squamous cellcarcinoma. Chromosome 4q18-32 region probably contains some tumorsuppressor genes related with the invasion and metastasis of lung squamous cellcarcinoma.Part two:Initiatory study of PTPN13 gene in invasion and metastasis of lungsquamous cell carcinomaMethods：Immunohistochemisty technology was applied to observe theexpression of PTPN13 in lung squamous cell carcinoma tissues and adjacentnormal lung tissues.Results：1、The positive expression rate of PTPN13 was significantly higher in adjacentnormal lung tissues than that in tumor tissues (P<0.05). The positive expressionrate of PTPN13 in lung squamous cell carcinoma was associated with clinicalstages, metastasis and pathological grade (P<0.05), but not associated with ageand gender.2、The positive expression rate of FAK was significantly lower in adjacentnormal lung tissues than in tumor tissues (P<0.05). The positive expression rateof FAK in lung squamous cell carcinoma was positively associated with clinicalstages, metastasis and pathological grade (P<0.05), but not associated with ageand gender.3、The positive expression rate of PTPN13 was higher than that of FAK in lung squamous cell carcinoma（P<0.05）.MaiMain Conclusions：1、PTPN13 gene may be a tumor suppressor gene related with the carcinogenesisas well as the invasion and metastasis of lung squamous cell carcinoma..2、In the function of PTPN13 gene as a tumor suppressor gene in thecarcinogenesis of lung squamous cell carcinoma, FAK gene phosphorylationmay play a important role.