Prognostic value of preoperative combined neutrophil, monocyte, and lymphocyte scores in patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A retrospective study.

BACKGROUND: In a multi-institutional clinical study, we assessed the prognostic significance of a novel indicator preoperative peripheral blood immune (PBIS) scores that combined ratios of preoperative lymphocyte, monocyte, and neutrophil of renal cell carcinoma (RCC) patients undergoing laparoscopic nephrectomy. METHODS: Between January 2014 and December 2019, 438 patients with RCC were retrospectively analyzed in three centers. We used X-tile software to obtain the optimum cut-off values for neutrophils, monocytes, and lymphocytes to classify the patients. To assess the relationship between PBIS score and overall survival (OS), and cancer-specific survival (CSS) in patients with RCC by Kaplan-Meier survival curves and Cox regression analyses. In addition, predictive OS and CSS nomograms were constructed. The discriminative ability of nomogram and predictive performance accuracy were verified with consistency index (C-index), calibration curves, receiver operating curve (ROC) curves, decision curve analysis (DCA) curves, and time-dependent ROC curves. RESULTS: The optimum cutoff values for monocytes, lymphocytes, and neutrophils were 0.46, 1.01, and 4.50, respectively. We divided patients into four subgroups according to PBIS scores, which were significantly associated with M-stage (p = 0.008), T-stage (p < 0.001), N-stage (p = 0.006), and AJCC stage (p < 0.001). Multivariate Cox regression analysis revealed that RCC patients with lower PBIS scores showed a worse postoperative prognosis and served as an independent predictor of OS (p = 0.002) and CSS (p < 0.001). Ultimately, the nomograms based on PBIS scores demonstrated excellent predictive performance for OS (C-index: 0.770) and CSS (C-index: 0.828) through the analysis of calibration curves, ROC curves, DCA curves, and time-dependent ROC curves. CONCLUSION: PBIS score served as novel and effective predictor to accurately predict OS and CSS in patients with RCC receiving laparoscopic nephrectomy.

DNMT3B-mediated FAM111B methylation promotes papillary thyroid tumor glycolysis, growth and metastasis.

Over the past decades, the incidence of thyroid cancer (TC) rapidly increased all over the world, with the papillary thyroid cancer (PTC) accounting for the vast majority of TC cases. It is crucial to investigate novel diagnostic and therapeutic targets for PTC and explore more detailed molecular mechanisms in the carcinogenesis and progression of PTC. Based on the TCGA and GEO databases, FAM111B is downregulated in PTC tissues and predicts better prognosis in PTC patients. FAM111B suppresses the growth, migration, invasion and glycolysis of PTC both in vitro and in vivo. Furthermore, estrogen inhibits FAM111B expression by DNMT3B methylation via enhancing the recruitment of DNMT3B to FAM111B promoter. DNMT3B-mediated FAM111B methylation accelerates the growth, migration, invasion and glycolysis of PTC cells. In clinical TC patient specimens, the expression of FAM111B is inversely correlated with the expressions of DNMT3B and the glycolytic gene PGK1. Besides, the expression of FAM111B is inversely correlated while DNMT3B is positively correlated with glucose uptake in PTC patients. Our work established E2/DNMT3B/FAM111B as a crucial axis in regulating the growth and progression of PTC. Suppression of DNMT3B or promotion of FAM111B will be potential promising strategies in the estrogen induced PTC.

[Expression of microRNA-223 and its clinicopathologic correlation in diffuse large B-cell lymphoma].

OBJECTIVE: To study the expression of miR-223 in diffuse large B cell lymphoma (DLBCL) with correlation of histoloigcal subtypes and clinical prognosis. METHODS: A total of 45 cases of DLBCL were investigated by immunohistochemistry (EnVision method) for CD20, CD3, CD10, bcl-6 and MUM-1. The cases were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans' algorithm. Agilent Human miRNA Microarray 16.0 was used to detect the expression of micro-RNAs in paraffin-embedded tissue of 24 cases of DLBCL that had available clinical follow-up. The expression levels of miR-223 were examined by TaqMan real-time reverse transcription polymerase chain reaction (real-time RT-PCR). Fourteen cases of reactive lymph node were selected as control. RESULTS: Among 45 cases of DLBCL, 16 cases (35.6%) were GCB and 29 cases (64.4%) were non-GCB subtypes. The expression levels of miR-223 measured by real-time RT-PCR were 19.8 and 15.8 in GCB and non-GCB subgroups, respectively (P = 0.236). The expression of miR-223 was up-regulated in DLBCL with 17.2 folds of increase over that of the reactive lymph nodes (P = 0.014). The overexpression of miR-223 was significantly correlated with a longer overall survival (P = 0.011). Multivariate Cox proportional hazard regression analysis identified the following independent poor prognostic factors: low expression of miR-223 (RR = 5.445, 95%CI, 1.555 - 19.068, P = 0.008), abnormal level of LDH (RR = 3.974, 95%CI, 1.191 - 13.266, P = 0.025) and IPI ≥ 3 (RR = 4.044, 95%CI, 1.233 - 13.264, P = 0.021). CONCLUSIONS: The expression of miR-223 has no relationship with the immunophenotypes of DLBCL. As a potential prognostic biomarker, overexpression of miR-223 correlates with a longer OS of patients with DLBCL.

[Significance of microRNA-146b-5p in diffuse large B-cell lymphoma and its relationship with risk assessment].

OBJECTIVE: To study the expression of miR-146b-5p in diffuse large B cell lymphoma (DLBCL), and its relationship with risk assessment. METHODS: 62 cases of nodal DLBCL with follow-up data were collected from Shanxi Cancer Hospital, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, Bcl-6 and MUM1. The DLBCLs were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans'algorithm. Agilent Human miRNA Microarray 16.0 was used to select the miRNAs on paraffin-embedded tissues of 24 DLBCL cases. A TaqMan real-time polymerase chain reaction (RT-PCR) method was performed on 62 nodal DLBCL cases to validate the expression levels of miR-146b-5p.11 cases with reactive lymph node were elected as control. RESULTS: In 62 cases of DLBCL, 35.5% of cases were GCB and 64.5% non-GCB subtypes, the expression of miR-146b-5p in GCB was 3.2 times as much as non-GCB subtypes (P = 0.006). The expression of miR-146b-5p was up-regulated in DLBCL, and expression level of miR-146b-5p was 5.4 times as much as reactivated lymph node. In 62 cases of DLBCL, 43.5% cases were recurrence-free and 56.5% recurrence. The expression of miR-146b-5p was remarkably up-regulated in recurrence-free group compared with recurrence group (P = 0.004). Moreover, high expression levels of miR-146b-5p in DLBCL were found to be associated with longer relapse-free survival (P = 0.005), but not for overall survival. Multivariate COX proportional hazard regression analysis revealed that low expression of miR-146b-5p (P = 0.004) and IPI ≥ 3(P = 0.011) were independent poor prognostic factors in 62 cases of DLBCL. CONCLUSIONS: The expression of miR-146b-5p was up-regulated in recurrence-free group, and its higher expression levels in DLBCL were associated with improved relapse-free survival. Our results suggested that miR-146b-5p might be one of markers for risk assessment.