Xiaobin Gu

Prognostic significance of neutrophil-to-lymphocyte ratio in prostate cancer: evidence from 16,266 patients

This study was aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa). A meta-analysis including 14 publications (15 cohorts) with 16,266 patients was performed to evaluate the association between NLR and overall survival (OS), progression-free survival (PFS)/recurrence-free survival (RFS) in PCa using hazard ratio (HR) and 95% confidence intervals (95% CI). The combining data showed that increased NLR predict poor OS (HR = 1.38, 95%CI: 1.22–1.56) and PFS/RFS (HR = 1.24, 95%CI 1.05–1.46) in PCa. Stratified analysis by PCa type, sample size, ethnicity and NLR cut-off value revealed that NLR showed consistent prognostic value in metastatic castration-resistant prostate cancer (mCRPC) patients and predict poor PFS/RFS in Asians, but not in Caucasians. These statistical data suggested that increased NLR could predict poor prognosis in patients with PCa.

Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: evidence from 3,430 patients

This study was designed to explore the association between elevated platelet to lymphocyte ratio (PLR) and prognosis of patients with non-small cell lung cancer (NSCLC) by meta-analysis. A total of 11 studies with 3,430 subjects were included and the combined hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated. The data showed that elevated PLR predicted poor overall survival (OS) (HR = 1.42; 95% CI: 1.25–1.61, p < 0.001; I2 = 63.6, Ph = 0.002) and poor disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.19; 95% CI: 1.02–1.4, p = 0.027; I2 = 46.8, Ph = 0.111). Subgroup analysis showed elevated PLR did not predict poor OS in patients included in large sample studies (HR = 1.44; 95% CI: 0.94–2.21, p = 0.098) whereas petients with Caucasian ethnicity (HR = 1.59; 95% CI: 1.27–1.98, p < 0.001) and PLR cut-off value >180 (HR = 1.61; 95% CI: 1.3–1.99, p < 0.001) had enhanced prognostic efficiency for OS. Subgroup analysis also demonstrated that high PLR did not predict poor DFS/PFS in Asian patients. In conclusion, our meta-analysis suggested that elevated PLR was associated with poor OS and DFS/PFS in NSCLC. In addition, high PLR especially predicted poor OS in Caucasians but had no association with poor DFS/PFS in Asians.

Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer.

The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1–1.52, p = 0.001; I2 = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88–2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC.

Elevated Platelet to Lymphocyte Ratio Is Associated with Poor Survival Outcomes in Patients with Colorectal Cancer.

Platelet to lymphocyte ratio (PLR) is a parameter reflecting inflammatory responses in patients with cancer. Several studies have investigated the prognostic value of PLR in patients with colorectal cancer (CRC); however, the results are controversial. Thus, we carried out a meta-analysis to evaluate the association between PLR and CRC prognostication. Relevant articles were retrieved through PubMed, Embase, and Web of Science, and pooled hazard ratio (HR) and 95% confidence interval (CI) were computed by using STATA V.12.0. Both the random-effects model and fixed-effects model were utilized. A total of 13 studies (14 cohorts) with 8,601 patients were included in the meta-analysis. Pooled HRs and 95% CIs demonstrated that increased PLR predicted poor overall survival (OS) (HR = 1.81, 95%CI:1.42–2.31, p<0.001; I2 = 65%, Ph = 0.002), disease-free survival (DFS) (HR = 1.84, 95%CI:1.22–2.76, p = 0.003; I2 = 78.3%, Ph<0.001) and recurrence-free survival (RFS) (HR = 1.84, 95%CI:1.41–2.41, p<0.001; I2 = 0, Ph = 0.686), although this was not the case for cancer-specific survival (CSS) (HR = 1.75, 95%CI:0.59–5.17, p = 0.309; I2 = 66.2%, Ph = 0.085) or time to recurrence (TTR) (HR = 1.21 95%CI:0.62–2.36, p = 0.573;I2 = 58.4%, Ph = 0.121). Subgroup analysis showed that PLR enhanced the prognostic value for OS in Caucasian patients, in small sample studies and for metastatic disease; however, this was not the case with rectal cancer. Furthermore, elevated PLR predicted reduced DFS in Caucasians and not in Asians. In conclusion, our meta-analysis showed that high PLR was a significant biomarker for poor OS, DFS, and RFS in patients with CRC; however, it had no association with CSS or TTR.

Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation

Aldo-keto reductase 1C3(AKR1C3) is an enzyme involved in prostaglandins metabolism. Studies suggest that AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer, yet the role of AKR1C3 in prostate cancer cells radiation resistance has not yet been clarified. In our study, we established a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145 and its control cell line (Control). We conducted colony formation assay to determine the role of AKR1C3 in radioresistance and we used its chemical inhibitor to detect whether it can restored the sensitivity of the acquired tumor cells. Flow cytometry assay was carried out to detect IR-induced ROS accumulation. Elisa was adopted to dedect the concentration of PGF2α in the suspension of the cells after 6GY radiation. Western blotting was used to dedect the MAPK and PPAR γ. The results demonstrated that overexpression of AKR1C3 in prostate cancer can result in radioresistance and suppression of AKR1C3 via its chemical inhibitor indocin restored the sensitivity of the acquired tumor cells. According to the flow cytometry assay, ROS was decreased by 80% in DU145-over cells. Also overexpression of AKR1C3 could result in the accumulation of prostaglandin F2α (PGF2α), which can not only promote prostate cancer cell s proliferation but also could enhance prostate cancer cells resistance to radiation and activated the MAPK pathway and inhibited the expression of PPARγ. In conclusion, we found that overexpression of AKR1C3 significantly enhanced human prostate cancer cells resistance to radiation through activation of MAPK pathway.

Prognostic significance of osteopontin expression in gastric cancer: a meta-analysis

Background Accumulated studies have exploited the association between osteopontin (OPN) expression and survival of patients with gastric cancer (GC), however, the results were controversial. Thus, we performed a meta-analysis, aiming to investigate the prognostic role of OPN for GC patients and to explore the association between OPN and clinicalpathological features of GC. Results A total of ten studies involving 1775 patients were included in final meta-analysis. Of the included studies, nine were conducted on Asian patients and one was performed on Caucasian patients. Regarding OPN detection, immunohistochemistry (IHC) was used on tissue specimens in eight studies and enzyme linked immunosorbent assay (ELISA) was used on plasma specimens in two studies. The pooled data showed that high OPN expression was correlated with poor OS (HR = 1.59, 95% CI: 1.15–2.22, p = 0.006). Subgroup analyses demonstrated that OPN had enhanced prognostic value for Asian patients (HR = 1.64, 95% CI = 1.11–2.41, p = 0.012) and for patients receiving surgical resection (HR = 1.6, 95% CI = 1.04–2.48, p = 0.034). In addition, the results also showed that elevated OPN expression was associated with lymph node metastasis, TNM stage, depth of invasion, tumor size and distant metastasis in GC. Methods Relevant studies were retrieved through PubMed, Embase and Web of Science. Combined hazard ratio (HR) and 95% confidence interval (CI) were calculated to assess the association between OPN and overall survival (OS). Subgroup analyses and publication bias were also conducted. Conclusions OPN overexpression was correlated with poor OS and clinical features reflecting high aggressiveness in patients with GC. OPN was a promising prognostic biomarker for GC.

Increased programmed death ligand-1 expression predicts poor prognosis in hepatocellular carcinoma patients

Purpose Accumulating studies have investigated the prognostic and clinical significance of programmed death ligand-1 (PD-L1) expression in patients with hepatocellular carcinoma (HCC); however, the results were conflicting and inconclusive. We conducted a meta-analysis to combine controversial data to precisely evaluate this issue. Methods Relevant studies were thoroughly searched on PubMed, Web of Science, and Embase until April 2016. Eligible studies were evaluated by selection criteria. Hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the prognostic role of PD-L1 for overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Odds ratio (OR) with 95% CI were selected to assess the relationship between PD-L1 and clinicopathological features of HCC patients. Publication bias was tested using Begg’s funnel plot. Results A total of seven studies published from 2009 to 2016 were included for meta-analysis. The data showed that high PD-L1 expression was correlated to shorter OS (HR =2.09, 95% CI: 1.66–2.64, P<0.001) as well as poor DFS/RFS (HR =2.3, 95% CI: 1.46–3.62, P<0.001). In addition, increased PD-L1 expression was also associated with tumor differentiation (HR =1.51, 95% CI: 1–2.29, P=0.05), vascular invasion (HR =2.16, 95% CI: 1.43–3.27, P<0.001), and α-fetoprotein (AFP; HR =1.46, 95% CI: 1–2.14, P=0.05), but had no association with tumor stage, tumor size, hepatitis history, sex, age, or tumor multiplicity. No publication bias was found for all analyses. Conclusion This meta-analysis revealed that overexpression of PD-L1 was predictive for shortened OS and DFS/RFS in HCC. Furthermore, increased PD-L1 expression was associated with less differentiation, vascular invasion, and AFP elevation.

BRCA2 mutations should be screened early and routinely as markers of poor prognosis: evidence from 8,988 patients with prostate cancer

The aim of this study was to focus on clinicopathological characteristics and prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 (BRCA2) gene mutation and to offer convincing evidence to consider BRCA2 mutation as a marker of poor prognosis in the molecular classification of PCa. We searched relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library databases to evaluate the differences in the overall survival (OS) and cancer-specific survival (CSS) between BRCA2 mutation carriers and non-carriers in patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers in total from 10 studies in our meta-analysis. The results showed that carrying a BRCA2 mutation was correlated with a reduced CSS and OS when compared with that of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval (CI): 2.10–3.06, P < 0.001) and 2.21 (95% CI: 1.64–2.99, P < 0.001), respectively. The results also demonstrated that BRCA2 mutation-carriers harbored a higher Gleason Score (GS) (> 7), TNM stage (> T3, N1, M1), and risk level than non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor survival outcomes in patients with prostate cancer, especially in those undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.

The role of definitive chemoradiotherapy versus surgery as initial treatments for potentially resectable esophageal carcinoma

BackgroundWe performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer.MethodsTo assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (N = 2071; dCRT = 869 and surgery = 1202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC).ResultsThe 2-year (OR = 1.199, 95% CI 0.922–1.560; P = 0.177) and 5-year overall survival (OS) rates (OR = 0.947, 95% CI 0.628–1.429; P = 0.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (OR = 1.397, 95% CI 0.740–2.638; P = 0.303) or stage II–III (OR = 0.418, 95% CI 0.022–7.833; P = 0.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (OR = 0.226, 95% CI 0.044–1.169; P = 0.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (OR = 1.522, 95% CI 1.035–2.238; P = 0.033). dCRT and surgery led to similar 5-year progression-free survival rates (OR = 1.06, 95% CI 0.79–1.42; P = 0.70).ConclusionsdCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC.

Partial stereotactic ablative boost radiotherapy in bulky non-small cell lung cancer: a retrospective study

Purpose Bulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC. Patients and methods From December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated. Results Median follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects >CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P<0.05). BED in the tumor center could reach 107.3 Gy (93.2–132 Gy). Patients with B90≥65% achieved a higher local control rate than those with B90<65% (P=0.010). Conclusion This retrospective study suggests that P-SABR is feasible and well tolerated in bulky NSCLC. Local control rate is encouraging, especially for the B90≥65% group, which may due to the ability of P-SABR to optimize BED with equivalent toxicity.