High expression of polo-like kinase 4 predicts worse progression-free survival in diffuse large B cell lymphoma patients treated with R-CHOP

在接受 R-CHOP 方案治疗的弥漫性大 B 细胞淋巴瘤患者中,polo 样激酶 4 的高表达预示着更差的无进展生存期。

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Abstract

BACKGROUND: Polo-like kinase 4 (PLK4) has been shown to be a tumor-promoting factor with multiple impacts on cancer growth, invasiveness, and treatment sensitivity. The current study aimed to investigate the expression of PLK4 in diffuse large B-cell lymphoma (DLBCL) versus control tissues and its relationship with disease features and prognosis in DLBCL patients undergoing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) treatment. METHODS: Ninety-seven DLBCL patients who received R-CHOP treatment were retrospectively included, and the lesion tissue was retrieved and subjected to quantitative polymerase chain reaction (qPCR) for PLK expression determination. Another 30 control tissues (reactive lymphoid tissue) were also subjected to qPCR. RESULTS: PLK4 expression was greater in DLBCL tissue than in reactive lymphoid tissue (nearly 3-fold change, P < 0.001). PLK4 in DLBCL was correlated with increased Ann Arbor stage (P = 0.038), lactate dehydrogenase abnormality (P = 0.031), international prognostic index (IPI) score (P = 0.002) and IPI risk stratification (P = 0.001). After cutoff by quartiles, PLK4 ≥ 50% quantile (P = 0.040) and PLK4 ≥ 75% quantile (P = 0.021) were correlated with shorter progression-free survival (PFS), but PLK4 ≥ 25% quantile was not (P = 0.236); PLK4 ≥ 25% quantile (P = 0.349), PLK4 ≥ 50% quantile (P = 0.126), and PLK4 ≥ 75% quantile (P = 0.090) were not correlated with overall survival (OS). Moreover, threshold by best cutoff value (3.755), PLK4 > 3.755 was correlated with both worse PFS (P = 0.002) and OS (P = 0.036). After adjustment via multivariate Cox regression, PLK4 > 3.755 was independently correlated with PFS (hazard ratio = 3.900, P = 0.023). CONCLUSIONS: High PLK4 expression can reflect severe disease conditions and predict poor PFS in DLBCL patients undergoing R-CHOP treatment. This study sheds a light on the potency of PLK4 as a prognostic biomarker for DLBCL management. However, more large-sample-sized and multiple regional studies are needed for verification in the future.

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