Gemin3Gene Polymorphism In The MicroRNA Processing Is Associated With Aggressive Lymphoma Clinical Features And Prognosis

Objective: Lymphoma is one of the hematological malignancies. Now,the incidence of lymphoma is increasing year by year, leading to thatlymphoma has entered the ranks of the top ten cancers. It is a highlyheterogeneous disease including prognostic differences. For the peripheral T-cell lymphoma and diffuse large B-cell lymphoma, IPI scores used to assessprognosis are now can not meet the clinical demands. We may explore newmark that can provide new reference for prognosis to guide individualizedtreatment. MicroRNA (miRNA) is a small non-coding RNA which iscomposed of about22nucleotides. MiRNA can regulate the one third of thehuman gene expression at post-transcriptional levels. Single nucleotidepolymorphism (SNP), the variation caused by a single nucleotidepolymorphism in the DNA sequence at genomic levels, is the most commongenetic variation of the human genome. The SNPs in the miRNA processingmay change the expression level and function of miRNA and affect generegulation of miRNA, which have associated with various of tumorformation, progression and prognosis. In this study, for the first time weanalyzed the genetic variations of Gemin3in the miRNA processing toexplore the association with clinical characteristics and prognosis of theperiheral T-cell lymphoma and that of diffuse B-cell lymphoma.Methods:1Research object: Patients: the blood samples were collected at theFourth Hospital of Hebei Medical University from non-Hodgkin’s lymphomapatients between January2000and January2008. The clinical information ofall patients was relatively perfect, including ages, survival status and so on.The control groups were60cases health people who accepted medical examination in the same period.2DNA extraction: Genomic DNA was extracted by protease K digestionfollowed by a salting out procedure from the blood of non-Hodgkin’slymphoma patients and the normal control group people, and then the DNAwas frozen immediately in refrigerator until used.3PCR (Polymerase chain reaction): The target gene fragment wasamplified by PCR and it was confirmed by gel electrophoresis. The PCRamplification product was sent to the Shanghai Generay Biotech CO., Ltd,where Gemin3gene polymorphism rs197412were genotyped by ligasedetection reaction (LDR) method.4Statistical analysis: All statistical analyses were performed by usingSPSS17.0statistical software. P <0.05, was considered statistically significant.By using χ2test, we analyzed the genotype frequencies of rs197412. Survivalanalysis was used to evaluate the relationship of rs197412genotype andlymphoma prognosis. Univariate analysis: the Kaplan-Meier method and Log-Rank test; Multivariate survival analysis: Cox regression analysis.Results:1In the normal control group, TT genotype have24cases, CC+CTgenotype have36cases; In the lymphoma patients group, the TT genotypehave45cases, CC+CT genotype have60cases. P=0.720, we may think thatrs197412genotype distribution difference was not statistically significant.2In the clinical features of all lymphoma patients (age, sex, stage, bonemarrow status, LDH levels, lymph nodes size), CC+CT genotype and TTgenotype frequencies was no significant difference, P>0.05.3Univariate analysisIn all lymphoma patients,5-year survival rates of CT+CC genotype andTT genotype were18.3%,40.0%, respectively. P=0.007(<0.05), thedifference was statistically significant.LDH, stage, bone marrow status, all P <0.05, the difference wasstatistically significant.4Multivariate analysis We collected the four factors (genotype, bone marrow, LDH, stage) intoCOX regression model for multivariate analysis.The multivariate analysis showed the relationship between rs197412genotype and prognosis of all the lymphoma patients, P=0.003，RR=2.138，95%CI=1.303-3.508. The patients with CC+CT genotype had risk of death2.138times than the TT genotype. The rs197412genotype may be theindependent prognostic impact factor.LDH and prognosis of lymphoma patients, P=0.049, LDH affectlymphoma prognosis.Stage and prognosis of lymphoma patients, P=0.006, stage affectlymphoma prognosis.This study showed that bone marrow status was not associated withlymphoma patients prognosis (P=0.716).Conclusions:1The prognosis of the diffuse large B-cell lymphoma and peripheral T-cell lymphoma patients is affected by rs197412genotype. TT genotypepatients had longer survival time than the CC+CT genotype and thedifference showed statistically significant.2In the different clinical characteristics (including age, gender, LDH,stage, bone marrow status, lymph node size) of the aggressive lymphomapatients, the rs197412genotype frequencies were no significant differences.