Mutation of proviral integration site for Moloney murine leukemia virus 1 in diffuse large B-cell lymphoma and its clinical significance / 白血病·淋巴瘤

ABSTRACT

Objective:To investigate the mutation of proviral integration site for Moloney murine leukemia virus 1 (PIM1) in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:Paraffin-embedded tissues of 38 DLBCL patients surgically resected at Shiyan Taihe Hospital from January 2016 to March 2022 were collected. The mutation of PIM1 gene was detected by polymerase chain reaction (PCR)-Sanger sequencing. The DLBCL-related DUKE, DFCI and TCGA datasets in the cBioPortal database were screened to collect information on PIM1 gene mutation and expression and clinical prognosis. Patients were divided into PIM1 mutation-positive group and PIM1 mutation-negative group, and the differences in clinicopathological characteristics, tumor mutational burden (TMB), microsatellite instability (MSI) levels and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used for survival analysis, and univariate and multivariate survival analyses were performed using Cox proportional hazards model.Results:The PIM1 mutation rates of DLBCL patients in DUKE, DFCI, TCGA datasets and Shiyan Taihe Hosipital were 14.3% (96/673), 26.3% (26/99), 19.5%(8/41) and 28.9% (11/38), respectively, in which mutation site and mutation form were more commonly found in exon 4 and missense mutations. There were statistical differences in the PIM1 mutation rate among DLBCL patients with different age (DUKE dataset) and cell of origin (COO) classification (DFCI dataset) ( χ2 values were 8.22 and 4.40, both P<0.05). Compared with PIM1 mutation-negative group, the PIM1 mutation-positive group had a higher TMB in DUKE, DFCI and TCGA datasets (all P<0.05). In DUKE and DFCI datasets, the OS of PIM1 mutation-positive group was worse than that of PIM1 mutation-negative group (both P<0.05), and multivariate Cox regression analysis showed that PIM1 gene mutation-positive was an adverse prognostic factor of OS (DUKE dataset HR = 1.661, 95% CI 1.151-2.396, P = 0.007; DFCI dataset HR = 2.074, 95% CI 1.031-4.172, P =0.041). Conclusions:PIM1 gene mutation may be related to the poor prognosis of DLBCL patients.