Xintao Li

MicroRNAs as prognostic molecular signatures in renal cell carcinoma: a systematic review and meta-analysis

This is a systematic review of studies investigating the prognostic value of different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant studies were identified, with a total of 2578 subjects. We found that elevated expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630, and miR-497 was associated with a poor prognosis in RCC patients. Conversely, decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187, miR-129–3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis. We performed meta-analyses on studies to address the prognostic value of miR-21, miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.28–4.08), cancer specific survival (CSS; HR, 4.16; 95% CI, 2.49–6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16–3.98). The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35; 95% CI, 0.15–0.85), OS (HR, 0.45; 95% CI, 0.30–0.69), and DFS (HR 0.30; 95% CI, 0.18–0.50). Our comprehensive systematic review reveals that miRs, especially miR-21 and miR-126, could be promising prognostic markers and useful therapeutic targets in RCC.

Prevalence and Characterization of Somatic Mutations in Chinese Aldosterone-Producing Adenoma Patients

AbstractRecently somatic mutations of KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been identified in patients with aldosterone-producing adenoma (APA). The present study sequenced the DNA in the tissues and blood samples from Chinese patients with APA for KCNJ5, ATP1A1, ATP2B3, and CACNA1D gene mutations.Among the 114 patients, 86 (75.4%) were identified with KCNJ5 somatic mutations, including 3 previously reported (G151R, L168R, T158A) and 2 other unreported mutations. One patient presented with both a point mutation (E147) and an insertion mutation, whereas another had a 36-base duplication, G153_G164dup. No mutation of ATP1A1 and ATP2B3 in the known hotspots was identified and only 1 male patient was detected with a novel CACNA1D mutation, V748I. Unlike other studies, male and female patients had similar KCNJ5 mutation rates (76.9% vs 74.2%). Mutation carriers were younger and had lower preoperative potassium level, whereas male (but not female) mutation carriers had higher preoperative plasma aldosterone concentration and preoperative blood pressures. Mutation carriers also had higher LV mass index (LVMI) than nonmutation carriers. After surgery, LVMI improved significantly in the KCNJ5 mutation group but not in the nonmutation group. The mRNA expression of KCNJ5, CYP11B2, and ATP2B3 was higher in the KCNJ5-mutated APA tissues. Functional characterization of the 2 novel KCNJ5 mutations showed that they were associated with decreased proliferation, membrane depolarization, elevated secretion of aldosterone, and increased expression of CYP11B1 and CYP11B2.In conclusion, Chinese APA patients appear to have a high frequency of somatic KCNJ5 mutation. Mutation prevalence rates are similar among men and women and 2 novel mutations are identified. KCNJ5-mutated patients benefit more from surgical resection of APA than nonmutated patients.

The Impact of Diabetes Mellitus on Renal Cell Carcinoma Prognosis: A Meta-Analysis of Cohort Studies

AbstractPrevious studies that investigated the relationship between DM and survival in renal cell carcinoma (RCC) patients reported inconsistent findings. Hence, we conducted a meta-analysis to obtain a more precise evaluation of the prognostic significance of DM in RCC. A systematic review was conducted with PubMed, Embase, and Web of Science to identify relevant articles that evaluated the effect of DM on RCC patients. Based on the inclusion and quality assessment criteria, 18 studies were eligible for the meta-analysis. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were calculated by standard meta-analysis techniques. The results suggested that DM was associated with poor OS (HR 1.56, 95% CI, 1.35–1.81, P < 0.001), poor CSS (HR 2.03, 95% CI, 1.37–3.01, P < 0.001), and poor RFS (HR 1.73, 95% CI, 1.25–2.39, P = 0.012). In addition, for patients with localized RCC, patients with clear cell RCC, or patients receiving nephrectomy, DM was associated with both poor OS and CSS by subgroup analyses. Our study revealed that there was a significant negative impact of DM on OS, CSS, and RFS in RCC patients. Therefore, more attention should be paid to RCC patients with preexisting DM because of their poor prognosis.

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.

MicroRNA-185 inhibits cell proliferation and induces cell apoptosis by targeting VEGFA directly in von Hippel-Lindau-inactivated clear cell renal cell carcinoma.

OBJECTIVES The von Hippel-Lindau (VHL) gene acts as a tumor suppressor in most clear cell renal cell carcinomas (ccRCCs). Tumor growth in ccRCCs relies on many factors that result from the loss of VHL. This study aims to identify new microRNAs with therapeutic potential for VHL-inactivated ccRCCs. MATERIALS AND METHODS We used 786O, A498 (VHL inactivated), and Caki-1 (VHL intact) ccRCC cell lines and 40 ccRCC samples and their adjacent nontumor tissues to measure the expression of microRNA-185 (miR-185) by real-time quantitative polymerase chain reaction. Overexpression or knockdown of VEGFA expression in renal cancer cells was fulfilled by transfecting expression plasmids or small interfering RNAs. Overexpression of miR-185 in ccRCC cell lines was fulfilled by transfecting chemically synthesized miR-185 mimics. The effects of miR-185 on ccRCC cell lines were detected by MTS assay, colony formation assay, and flow cytometric analysis. RESULTS Compared with adjacent nontumor renal tissues, miR-185 expression levels decreased significantly in ccRCC tissues. The expression of miR-185 had a negative correlation with tumor size, Fuhrman grade, and TNM staging. Luciferase assay showed that VEGFA was a direct target gene of miR-185. The overexpression of miR-185 significantly inhibited cell proliferation and induced cell apoptosis by down-regulating VEGFA expression in VHL-inactivated ccRCC cells. CONCLUSIONS Our results suggest that the miR-185, as a tumor suppressor, plays a pivotal role by inhibiting VEGFA in VHL-inactivated ccRCC.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Localized and Advanced Prostate Cancer: A Systematic Review and Meta-Analysis

Objective and Background Increasing evidence suggests that inflammation plays an essential role in cancer development and progression. The inflammation marker neutrophil–lymphocyte ratio (NLR) is correlated with prognosis across a wide variety of tumor types, but its prognostic value in prostate cancer (PCa) remains controversial. In the present meta-analysis, the prognostic value of NLR in PCa patients is investigated. Methods We performed a meta-analysis to determine the predictive value of NLR for overall survival (OS), recurrence-free survival (RFS), and clinical features in patients with PCa. We systematically searched PubMed, ISI Web of Science, and Embase for relevant studies published up to October 2015. Results A total of 9418 patients from 18 studies were included in the meta-analysis. Elevated pretreatment NLR predicted poor OS (HR 1.628, 95% CI 1.410–1.879) and RFS (HR 1.357, 95% CI 1.126–1.636) in all patients with PCa. However, NLR was insignificantly associated with OS in the subgroup of patients with localized PCa (HR 1.439, 95% CI 0.753–2.75). Increased NLR was also significantly correlated with lymph node involvement (OR 1.616, 95% CI 1.167–2.239) but not with pathological stage (OR 0.827, 95% CI 0.637–1.074) or Gleason score (OR 0.761, 95% CI 0.555–1.044). Conclusions The present meta-analysis indicated that NLR could predict the prognosis for patients with locally advanced or castration-resistant PCa. Patients with higher NLR are more likely to have poorer prognosis than those with lower NLR.

Prognostic value of CD44 expression in renal cell carcinoma: a systematic review and meta-analysis.

CD44 is a marker of cancer stem-like cells in renal cell carcinoma (RCC). However, the prognostic value of CD44 in RCC remains controversial. This study evaluated the correlation of CD44 expression with the clinicopathological features of RCC through a meta-analysis. We systematically searched PubMed, ISI Web of Science and Embase for relevant studies until February 2015. We collected and analysed data on clinical stage, Fuhrman grade, microvascular invasion, recurrence, five-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Twenty studies involving 1672 patients satisfied the inclusion criteria. Results showed that high CD44 expression in RCC was a poor prognostic marker for five-year OS (RR = 0.69, 95% CI 0.60–0.78) in a fixed-effects model and for five-year DSS (RR = 0.46, 95% CI 0.27–0.80) and five-year DFS (RR = 0.63, 95% CI 0.43–0.93) in a random-effects model. CD44 expression also correlated with Furhman grade (RR = 0.61, 95% CI 0.48–0.77), tumour recurrence (RR = 7.42, 95% CI 3.74–14.70) and MVI (Microvascular invasion) (RR = 3.63, 95% CI 1.97–6.71). This meta-analysis suggests that CD44 is a prognostic marker in RCC. High CD44 expression correlates with high Fuhrman grade, recurrence, MVI and poor prognosis.

Robot-assisted Laparoscopic Inferior Vena Cava Thrombectomy: Different Sides Require Different Techniques

BACKGROUND The safety and feasibility of robot-assisted laparoscopic inferior vena cava (IVC) thrombectomy (RAL-IVCTE) have been investigated in limited reports. OBJECTIVE To share our initial experience with RAL-IVCTE, as well as describe respectively the detailed techniques for RAL-IVCTE for left or right renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS From May 2013 to July 2014, 17 patients with RCC involving IVC tumor thrombus were admitted to our hospital. SURGICAL PROCEDURE For right RCC, the caudal IVC, left renal vein, and cephalic IVC were sequentially clamped. The IVC wall was cut, and the thrombus was removed. For left RCC, the left renal vein, which included the thrombus, was ligated with Endo-GIA. The caudal IVC, right renal artery, right renal vein, and cephalic IVC were sequentially clamped. MEASUREMENTS The detailed techniques for RAL-IVCTE for different sides were described and the perioperative outcomes recorded. RESULTS AND LIMITATIONS The operations were successfully performed without open conversion. Median operation time was 131min (100-150min) and 250min (190-275min) for the right and left RCC, respectively. Median estimated blood loss was 240ml (145-320ml). Median IVC blocking time was 17min (12-25min). For left RCC, median warm ischemia time for the right kidney was 18min (14-22min). A grade IV complication-bleeding from tributaries of the IVC-developed in one case and was successfully resolved with intraoperative endoscopic suture. CONCLUSIONS RAL-IVCTE is safe and feasible. For left RCC involving IVC thrombus, right renal warm ischemia time is necessary during the procedure, requiring a more advanced technical skill. The therapeutic effect and overall survival rate require further investigation with a larger sample size and longer follow-up. PATIENT SUMMARY Robot-assisted laparoscopic inferior vena cava thrombectomy is technically challenging but safe and feasible. The therapeutic effect needs further investigation.

The association of platelet count with clinicopathological significance and prognosis in renal cell carcinoma: a systematic review and meta-analysis.

Objective Elevated platelet count (PC), a measure of systemic inflammatory response, is inconsistently reported to be associated with poor prognosis in patients with renal cell carcinoma (RCC). We conducted a systematic review and meta-analysis to clarify the significance of PC in RCC prognosis. Methods PubMed, Embase, and Web of Science databases were searched to identify eligible studies to evaluate the associations of PC with patient survival and clinicopathological features of RCC. Results We analyzed 25 studies including 11,458 patients in the meta-analysis and categorized the included articles into three groups based on RCC stage. An elevated PC level was associated with poor overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87-2.67, P<0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48, P<0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI 2.41-10.73, P<0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34, P<0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, P<0.001) for metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, P = 0.038), CSS (HR 3.38, 95% CI 1.86-6.15, P<0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, P = 0.002) for clear cell RCC. Furthermore, an elevated PC level was significantly associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, P = 0.001), pathological T stage (OR 3.13, 95% CI 2.60-3.77, P<0.001), lymph node metastasis (OR 4.01, 95% CI 2.99-5.37, P<0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, P<0.001), Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, P<0.001), tumor size (OR 4.69, 95% CI 2.78-7.91, P<0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI 3.26-9.28, P<0.001). Conclusion An elevated PC level implied poor prognosis in patients with RCC and could serve as a readily available biomarker for managing this disease.

Prognostic Significance of Hypoxia-Inducible Factor Expression in Renal Cell Carcinoma: A PRISMA-compliant Systematic Review and Meta-Analysis.

AbstractThe prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis.PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1&agr; or HIF-2&agr; detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed.A total of 14 studies composed of 1258 patients for HIF-1&agr; evaluation and 619 patients for HIF-2&agr; evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1&agr; expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898–2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595–2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675–1.836, P = 0.674). Similarly, HIF-2&agr; expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667–3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566–1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1&agr; was significantly associated with poor OS (HR 2.014, 95% CI 1.206–3.363, P = 0.007) and the high cytoplasmic expression of HIF -2&agr; was significantly associated with poor CSS (HR 2.356, 95% CI 1.629–3.407, P = 0.000).The increased nuclear expression of HIF-1&agr; and cytoplasmic expression of HIF-2&agr; indicate unfavorable prognosis in RCC patients, which may serve as biomarkers for disease management.