The Clinical Value Of CpG Island Methylator Phenotype In Plasma Of Non-small Lung Cancer

Objective:T his study is aimed to detect the status of CpG island methylatorphenotype (CIMP) as a methylation mark er panel (inclu de p16IN K4a, MGMTand RAR-β) in plasma and tissue of non-small cell lu ng cancer (NSCLC)patients and nonmalignant diseases patients as control, and evaluate theclinical significance of CIMP and its association with the diagnosis andprognosis.Method:45paired samples of tumor tissue and corresponding adjacentnormal tissu es(distance>5cm or su rgically resected margin) were obtainedfrom NSCLC patients who had been treated with surgery at the firstaffiliated hospital of Dalian Medical University between2010and2011.Samples from25nonmalignant tu mor patients were u sed as matchedas controls. Blood samples (2ml) were collected in tu bes with K+-EDT A,and plasma was immediately separated after centrifu gation at3000rpm for10minu te and stored at-80℃u ntil u se. DNA was extracted from tissu e andplasma. Extracted DNA samples were su bjected to sodiu m bisu lfiteconversion, and then the bisu fite modified DNA samples was determined byMethylation specific PCR (MS-PCR). PCR produ cts were separated in2%agarose gels and visualized u nder UV illu mination. T he CIMP statu s of oursamples was classified as CIMP+(with≥2methylated genes) or CIMP-(with<2methylated genes). Data was analyzed thou gh the SPSS13.0.Result: For tumor tissue samples,29samples of NSCLC were classified asCIMP+, and16samples as CIMP-. And regarding plasma samples,24samples of NSCLC were classified as CIMP+, and21samples as CIMP-.22 samples were classified as CIMP+both in tu mor tissu e and plasma. Onesample was examined as CI MP+in nonmalignant tissu es and plasmas ascontrols. T here was no difference between CIMP and age, gender, smoking,T statu s, histological type, differentiation (P>0.05). For plasma samples,the significant difference was between CIMP and N statu s, TNM sta ge(P<0.05). T here was significant difference between tu mor tissu es of NSCLCand nonmalignant diseases (P<0.05). And for plasma, the same resu lt(P<0.05) was obtained. The CIMP statu s of tu mor tissu e and plasma fromNSCLC showed respectively good concordan ce (Kappa=0.59), especiallyfor Stage II. Follow-u p for1.5years fou nd that the prognosis differedsignificantly between the CIMP+and CIMP-of plasma (P<0.05). There wasno difference between CIMP of plasma in NSCLC and CEA, Cyfra21-1(P<0.05).Conclusion: CIMP in plasma may be served as a biomarker of earlydiagnosis, differential diagnosis and prognosis of NSCLC.