Yongpeng Xie

Prognostic role of lymphocyte to monocyte ratio for patients with cancer: evidence from a systematic review and meta-analysis

Inflammation influences cancer development and progression, and a low lymphocyte to monocyte ratio (LMR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in various cancers. Eligible studies were retrieved from PubMed, Embase and Web of Science databases. Overall survival (OS) was the primary outcome, cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) were secondary outcomes. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Fifty-six studies comprising 20,248 patients were included in the analysis. Overall, decreased LMR was significantly associated with shorter OS in non-hematological malignancy (HR: 0.59, 95% CI: 0.53–0.66; P < 0.001) and hematological malignancy (HR: 0.44, 95% CI: 0.34–0.56; P < 0.001). Similar results were found in CSS, DFS, RFS and PFS. Moreover, low LMR was significantly associated with some clinicopathological characteristics that are indicative of poor prognosis and disease aggressiveness. By these results, we conclude that a decreased LMR implied poor prognosis in patients with cancer and could serve as a readily available and inexpensive biomarker for clinical decision.

LncRNAs act as prognostic and diagnostic biomarkers in renal cell carcinoma: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to investigate the clinical values, including clinicopathology, prognosis, and diagnosis of different long non-coding RNAs (lncRNAs) in renal cell carcinoma (RCC). A total of 14 eligible studies, including 10 on clinicopathological features, 11 on prognosis, and 3 on diagnosis were identified. Results revealed that metastasis-associated lung adenocarcinoma transcript 1(MALAT1) expression was associated with tumor stage (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.63-7.36; p=0.001). The high expression of MALAT1 could be considered a biomarker of the early detection of lymph node metastasis and predictor of poor survival in RCC patients, who likely manifested short overall survival (OS; hazard ratio [HR], 2.97; 95% CI, 1.68-5.28; p<0.001). For diagnostic value, the pooled result showed that lncRNA maintained a sensitivity of 0.89 and specificity of 0.91 in RCC diagnosis, The area under the curve of 0.94 (95% CI, 0.92-0.96) for lncRNA in RCC diagnosis also indicated a significant advantage over other biomarkers. Our systematic review and meta-analysis demonstrated that lncRNAs could be considered biomarkers to detect lymph node metastasis and distant metastasis in early stages. LncRNAs could function as potential prognostic markers in RCC. LncRNAs could also display high accuracy for RCC diagnosis.

MicroRNAs with prognostic significance in bladder cancer: a systematic review and meta-analysis.

The aim of this study was to systematically review articles that investigated the prognostic significance of different microRNAs in bladder cancer (BC). We systematically searched PubMed, Web of Science, and Embase to identify relevant studies until March 2016. After screening, 26 studies that involved 2753 patients were included. Results suggested that many miRs expression aberration may predict prognosis in patients with BC. There are six miRs (miR-21, miR-143, miR-155, miR-200, miR-214, and miR-222) were reported by at least two studies, and we performed meta-analysis in the corresponding studies. Accordingly, we found that high miR-21 expression was associated with poor overall survival [OS; hazard ratio (HR) = 3.94, 95% CI 2.08–7.44]. High miR-143 expression was associated with poor progression-free survival (PFS; HR = 3.78, 95% CI 1.61–8.89). High miR-155 expression was associated with poor PFS (HR = 8.10, 95% CI 2.92–22.48). High miR-222 expression was associated with poor OS (HR = 3.39, 95% CI 1.10–10.41). Meanwhile, low miR-214 expression was correlated with poor RFS(HR = 0.34, 95% CI 0.22–0.53). Our comprehensive systematic review concluded that microRNAs, particularly miR-21, miR-143, miR-155, miR-214, and miR-222, could serve as meticulous follow-up markers for early detection of progression or recurrence and even useful therapeutic targets for the treatment in patients with BC.

Invasion of the urinary collecting system is an independent prognostic factor in pT3 renal cell carcinoma

OBJECTIVE To evaluate the prognostic significance of urinary collecting system invasion (UCSI) in pT3 renal cell carcinoma (RCC). PATIENTS AND METHODS Patients undergoing nephrectomy for renal masses with pathological stage T3 RCC at our institution from 2006 to 2014 were identified. The entire cohort was divided into 2 groups according to the presence of UCSI. Clinicopathological variables were collected and compared using Students t-test or chi-square test. Kaplan-Meier survival analysis and multivariate Cox regression were performed to determine the effect of UCSI on survival outcomes. RESULTS Of the 218 patients with pT3 RCC enrolled in this study, 68 (31.2%) presented with UCSI. The presence of UCSI was associated with higher rates of symptoms at diagnosis (P<0.001), larger tumor sizes (P = 0.004), higher Fuhrman grades (P = 0.018), lower proportions of perirenal fat invasion (P = 0.024), and higher probabilities of having tumor necrosis (P = 0.024) and positive lymph nodes (P<0.001). When compared with those without UCSI, patients with UCSI showed shorter estimated 5-year cancer-specific survival rates (33.5% vs. 55.8%, P<0.001) and 5-year progression-free survival rates (27.4% vs. 44.3%, P<0.001). Multivariate analysis revealed that UCSI was independently associated with poorer cancer-specific survival rates (hazard ratio = 1.76, 95% CI: 1.12-2.78, P = 0.015) and progression-free survival rates (hazard ratio = 1.82, 95% CI: 1.23-2.68, P = 0.003). CONCLUSION UCSI appears to be an independent prognostic factor of pT3 RCC and may be considered in future TNM systems to help stratify different prognoses. More attention should be paid to patients with pT3 RCC with UCSI and close follow-up is recommended to improve survival rates.

Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50–11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC.

Prognostic value of a systemic inflammatory response index in metastatic renal cell carcinoma and construction of a predictive model

Inflammation act as a crucial role in carcinogenesis and tumor progression. In this study, we aim to investigate the prognostic significance of systemic inflammatory biomarkers in metastatic renal cell carcinoma (mRCC) and develop a survival predictive model. One hundred and sixty-one mRCC patients who had undergone cytoreductive nephrectomy were enrolled from January 2006 to December 2013. We created a systemic inflammation response index (SIRI) basing on pretreatment hemoglobin and lymphocyte to monocyte ratio (LMR), and evaluated its associations with overall survival (OS) and clinicopathological features. Pretreatment hemoglobin and LMR both remained as independent factors adjusted for other markers of systemic inflammation responses and conventional clinicopathological parameters. A high SIRI seems to be an independent prognosis predictor of worse OS and was significantly correlated with aggressive tumor behaviors. Inclusion of the SIRI into a prognostic model including Fuhrman grade, histology, tumor necrosis and targeted therapy established a nomogram, which accurately predicted 1-year survival for mRCC patients. The SIRI seems to be a prognostic biomarker in mRCC patients. The proposed nomogram can be applied to predict OS of patients with mRCC after nephrectomy.

Prognostic role of urinary collecting system invasion in renal cell carcinoma: a systematic review and meta-analysis.

The relationship between urinary collecting system invasion (UCSI) and oncological outcomes in renal cell carcinoma (RCC) patients has attracted extensive attention recent years. However, the reports were inconsistent and remain controversial. Thus, we performed a systematic literature search of PubMed, Embase, Web of Science and The Cochrane Library databases to identify relevant studies up to June 2015 and conducted a standard meta-analysis of survival outcomes. 17 studies containing 9012 RCC patients satisfied the inclusion criteria. Pooled HRs for overall survival (OS) and recurrence-free survival (RFS) were 1.45 (95% CI, 1.26–1.66, P < 0.001) and 2.27 (95% CI, 1.54–3.34, P < 0.001), respectively. Further subgroup analysis suggested that UCSI was significant associated with poor cancer-specific survival (CSS) in stage T1–T2 RCC (HR = 2.05, 95% CI: 1.43–2.96, P < 0.001) but not in stage T3–T4 tumors (HR = 1.08, 95% CI: 0.63–1.85, P = 0.771). Current evidence revealed that UCSI has a significant negative impact on OS and RFS in RCC patients and could be used to predict CSS especially in localized RCC. Thus, RCC patients with UCSI should be paid more attention by clinician and pathologist and require close follow up for their poor prognosis.

Prognostic and Clinicopathological Significance of Survivin Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically searched PubMed, Web of Science, and Embase to identify relevant studies until December 2015 and conducted a standard meta-analysis. Based on the inclusion and exclusion criteria, a total of 12 studies, including 2051 patients, were eligible for further analysis. Results showed that high survivin expression in RCC was associated with poor OS (HR = 2.84, 95% CI 1.68–4.79), CSS (HR = 2.36, 95% CI 1.41–3.95), and PFS (HR = 2.20, 95% CI 1.58–3.08). Survivin expression was also correlated with TNM stage (RR = 2.75, 95% CI 2.21–3.44), pathological T stage (RR = 2.19, 95% CI 1.75–2.75), lymph node metastasis (RR = 2.28, 95% CI 1.61–3.25), distant metastasis (RR = 1.56, 95% CI 1.16–2.08), Fuhrman grade (RR = 2.81, 95% CI 2.29–3.45), tumor size (RR = 1.49, 95% CI 1.24–1.78). Our study suggested that survivin was a prognostic marker in RCC. High survivin expression was correlated with poor prognosis and more advanced clinicopathological features, and it could serve as a biomarker for disease management.

Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle transition, and diminished apoptosis

OBJECTIVES Dysregulated expression of miR-181a accompanies tumorigenesis in many human cancers. However, in clear cell renal cell carcinoma (ccRCC), the role of miR-181a remains unclear. The aim of this study was to investigate biological functions of miR-181a and its expression levels in ccRCC tissues and cancer cell lines. MATERIAL AND METHODS Expression levels of miR-181a in samples of ccRCC tumors and adjacent nontumor tissues from 42 patients as well as in 786-O, 769-P, A498, and CAKI-1 ccRCC cell lines were determined by quantitative real-time polymerase chain reaction. Potential targets of miR-181a were predicted using bioinformatic approaches and then verified by using the luciferase reporter assay. The effects of miR-181a on cell proliferation, colony formation, cell cycle progression, and apoptosis were investigated in ccRCC cell lines transfected with specific miR-181a mimic and inhibitor. RESULTS We found that miR-181a expression was up-regulated in ccRCC tissues and cell lines. The expression level of miR-181a significantly correlated with the tumor size, tumor/node/metastasis staging, and Fuhrman grade. Luciferase assays showed that KLF6 was a target of miR-181a. KLF6 expression was inversely correlated with the level of miR-181a. Overexpression of miR-181a led to reduced KLF6 mRNA and protein levels, whereas mutations of the potential miR-181a binding sites in the KLF6 gene abrogated this inhibitory effect. Furthermore, overexpression of miR-181a promoted proliferation and G1/S cell cycle transition, as well as inhibited apoptosis by down-regulating KLF6 in ccRCC cells. CONCLUSIONS miR-181a is up-regulated in ccRCC and may act as a tumor promoting factor by targeting KLF6 expression. Manipulating miR-181a may provide a beneficial effect in the treatment of ccRCC.

Reduced E-cadherin expression is correlated with poor prognosis in patients with bladder cancer: a systematic review and meta-analysis

The prognostic significance of E-cadherin expression in bladder cancer (BC) has been elevated for years, but published results remain controversial and inconsistent. We thus performed a systematic review and meta-analysis to determine the association between E-cadherin expression and BC prognosis. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases to identify eligible studies published until March 2017. On the basis of our inclusion and exclusion criteria, a total of 2,089 patients from 19 studies were eligible for final analysis. Our results showed that reduced E-cadherin expression in BC was associated with poor overall survival (hazard ratio [HR] = 2.73, 95% CI: 1.74–4.27, p < 0.001), poor progression-free survival (HR = 6.39, 95% CI: 3.48–11.73, p < 0.001), and poor recurrence-free survival (HR = 2.48, 95% CI: 1.68–3.64, p < 0.001). Moreover, reduced E-cadherin expression was significantly correlated with pathological T stage (T2-4 vs. Ta-1: risk ratio [RR] = 2.14, 95% CI: 1.70–2.71), metastasis (yes vs. no: RR = 1.68, 95% CI: 1.17–2.40), grade (3 vs. 1/2: RR = 1.58, 95% CI: 1.29–1.93), and carcinoma in situ (yes vs. no: RR = 1.68, 95% CI: 1.09–2.58). This meta-analysis suggested that reduced E-cadherin expression was associated with poor prognosis and advanced clinicopathological characteristics and can serve as a useful biomarker for the clinical management of BC.