High KIF2A expression predicts unfavorable prognosis in diffuse large B cell lymphoma.
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ABSTRACT:
SUBMITTER: Zhang Y
PROVIDER: S-EPMC5537331 | biostudies-other | 2017 Sep
REPOSITORIES: biostudies-other
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Project description:Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is a highly heterogeneous type of non-Hodgkin lymphoma. A number of studies have demonstrated that microRNA-130a (miR-130a) serves a role in the tumorigenesis and prognosis of numerous human tumors. However, to the best of our knowledge, the prognostic significance of miR-130a in PGI-DLBCL remains unknown. The present study explored the association between miR-130a and the clinical outcomes of PGI-DLBCL. Relative miR-130a expression was assessed by reverse transcription-quantitative PCR. Immunohistochemistry was used to detect expression levels of BCL-2, c-MYC, neprilysin, B-cell lymphoma 6 protein, PWWP domain-containing DNA repair factor 3A and proliferation marker protein Ki-67. A receiver operating characteristic curve was constructed to analyze the specificity and sensitivity of microRNA levels in the diagnosis of PGI-DLBCL. Survival curves were constructed using the Kaplan-Meier method. In the present study, miR-130a expression was notably higher in patients with PGI-DLBCL compared with in the controls (P<0.0001). miR-130a overexpression was closely associated with a high International Prognostic Index score (3–5) and drug resistance (P=0.017 and P=0.044, respectively). No significant difference in other clinical features was observed. Patients with increased expression levels of miR-130a had lower overall survival [hazard ratio (HR), 2.998; 95% CI, 1.347-6.673; P=0.007] and progression-free survival (HR, 3.325; 95% CI, 1.488-7.429; P=0.003) compared with patients who had lower expression levels of miR-130a. Furthermore, multivariate Cox regression analysis suggested that miR-130a was a negative prognostic parameter in PGI-DLBCL. Therefore, upregulation of miR-130a could become a potential prognostic marker for PGI-DLBCL. Additionally, further study of these results may have important guiding significance for the prognosis of patients with PGI-DLBCL in the clinical setting.
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Project description:AimsYin Yang 1 (YY1) is a multifunctional transcription factor that plays an important role in tumour development and progression, while its clinical significance in diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the expression and clinical implications of YY1 in DLBCL.MethodsYY1 expression in 198 cases of DLBCL was determined using immunohistochemistry. The correlation between YY1 expression and clinicopathological parameters as well as the overall survival (OS) and progression-free survival (PFS) of patients was analyzed.ResultsYY1 protein expression was observed in 121 out of 198 (61.1 %) DLBCL cases. YY1 expression was significantly more frequent in cases of the GCB subgroup than in the non-GCB subgroup (P = 0.005). YY1 was positively correlated with the expression of MUM1, BCL6, pAKT and MYC/BCL2 but was negatively associated with the expression of CXCR4. No significant relationships were identified between YY1 and clinical characteristics, including age, sex, stage, localization, and B symptoms. Univariate analysis showed that the OS (P = 0.003) and PFS (P = 0.005) of patients in the YY1-negative group were significantly worse than those in the YY1-positive group. Multivariate analysis indicated that negative YY1 was a risk factor for inferior OS (P < 0.001) and PFS (P = 0.017) independent of the international prognostic index (IPI) score, treatment and Ann Arbor stage. Furthermore, YY1 is more powerful for stratifying DLBCL patients into different risk groups when combined with MYC/BCL2 double-expression (DE) status.ConclusionsYY1 was frequently expressed in DLBCL, especially in those of GCB phenotype and with MYC/BCL2-DE. As an independent prognostic factor, YY1 expression could predict a favourable outcome in DLBCL. In addition, a complex regulatory mechanism might be involved in the interactions between YY1 and MYC, pAKT as well as CXCR4 in DLBCL, which warrants further investigation.
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