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Hypermethylation of Tip30in Ppromter Region and Its Association with Folfox Chemosensitivity of Colorectal Cancer

Author: MaLei
Tutor: LuoSuXia
School: Henan University
Course: Oncology
Keywords: TIP30gene Colorectal cancer (CRC) DNA methylation Chemotherapy
CLC: R735.3
Type: Master's thesis
Year: 2012
Downloads: 35
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Abstract


Background:Colorectal cancer (CRC) is the most common malignant disease in the world. The incidence ofCRC has increased in recent years and the mortality lies in the fourth among human malignancies,therecurrence and metastasis are the main reasons leading to the death of patients with CRC, correspondingly,costs of thearopy and care also increased significantly. The morbidity and mortality of colorectal cancerwill gradually arise in quite a long period of time in the future in China. Therefore, the ongoing research forcolorectal cancer has also been a medical focus on the domestic and international. Today.,thecomprehensive strategy should be made individually and acted as the direction of patients with colorectalcancer. Only standardized treatment, improved postoperative follow-up system and the acceleration of theresearch of tumor molecular markers is achieved, the patients with CRC can be treated individually andgain the maximize benefits. TIP30,a tumor suppressor gene (TSG), has been confirmed its relationship tothe carcinogenesis and the evolution of colorectal cancer in numerous studies. the data has also showed thatTIP30gene promoter methylation is the main cause of low TIP30expression and is closely correlated tothe sensitivity to chemotherapeutic drugs in colorectal cancer cell lines.Objective:The purpose of this study was to explore the relationship between the status of TIP30promotermethylation and clinicopathological features, prognosis and chemosensitivity in patients with colorectalcancer and it provide an evidence to that TIP30act as a prognostic and predictive indicator theoritically andprovide a new way for individualized treatment in patients with colorectal cancer.Material and methods:The methylation status of TIP30between230cases of patients with CRC and the paired normalcolorectal samples was detected using Bisulfite DNA sequencing (BSP) and methylation-specific PCR(MSP). Statistical analysis was carried out using the Statistical Package for Social Sciences(SPSS),version13.0, Chi-square test and Logrank Test were used to test the association between TIP30gene methylationand the clinicopathological features of patients (tumor gross type, tumor type, lymph node metastasis). Results:1In colorectal cancers, the rate of TIP30promoter methylation was35.22%and the rate ofadjacent tissue was17.39%, the difference was statistically significant (P <0.05).2The rate of TIP30promoter methylation in patients with colon cancer was28.57%and therate in patients with rectal cancer was40.80%, the difference was statistically significant (P <0.05).3the rate of TIP30promoter methylation in patients with lymph node metastasis was41.57%,while the rate in patients with lymph node metastasis-negative tumor was13.46%, the difference wasstatistically significant (P<0.05).4the rate of TIP30promoter methylation in phase II patients was18.03%, while the rate inphase III patients is28.99%, and the rate in phase IV patients is50.00%.there was no statistically differencebetween Phase II and III patients (P=0.144), and there was statistically different between patients in stageⅢ and Ⅳ, and there was a significantly difference between patients in Phase II and IV (P <0.05).5the rate of TIP30promoter methylation in patients with colorectal adenocarcinoma was33.54%, while the rate in patients with mucinous adenocarcinoma and other types was39.13%, there wasno significant difference between this two groups (P=0.416).6In100patients with advanced colorectal cancer, the response rate (PR+CR+SD) in patientswith colon cancer received modified FOLFOX6regimen was67.39%, the rate of patients with rectal cancerwas46.29%, there was a statistically difference between the two groups. In130cases of colorectal cancer,the median DFS in patients with colon cancer suffered postoperative adjuvant chemotherapy was28months, while the median DFS in patients with rectal cancer was30months, there was no significantdifference between the two groups (P=.4644).7in100patients with advanced colorectal cancer, the response rate in TIP30promotermethylation-positive patients receive modified FOLFOX6regimen was54%, while the rate in TIP30promoter methylation-negative patients was74%, there was a statistically significant difference betweenthe two groups (P <0.05). in130cases of colorectal cancer, the median DFS in TIP30promotermethylation-positive patients was25months, the median DFS in patients without TIP30promotermethylation was29months, there was not statistically different between the two groups.Conclusions: TIP30hypermethylation are associated with the location, stage, recurrence and metastasis oftumor and it has no correlation with its pathological characters. tumor location and TIP30promotermethylation status was associated with the disease control rate of chemotherapy in patients with advancedcolorectal cancer, while it only has trends in tumor location, TIP30promoter methylation status and theDFS received postoperative adjuvant chemotherapy, there is not statistically significant between them.theresults show that TIP30promoter methylation status is a poor prognosis indicator in patients with colorectalcancer and is expected to be a new prognostic indicator and a indicator to predict the efficacy ofchemotherapy to for individualized treatment in patients with colorectal cancer.

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