Comprehensive evaluation of NT5E/CD73 expression and its prognostic significance in distinct types of cancers.

BACKGROUND: CD73 is one of the critical component in the formation of immunosuppressive microenvironment in cancers. We aimed to provide an overview of the current status of CD73 expression and its relationship with clinicopathlogical features and prognosis in different cancers. METHODS: PubMed, Web of Science, EMBASE and Cochrane library were searched to identify the relevant studies. CD73 expression level in distinct cancers and its relationship with clinicopathlogical characteristics and prognosis were investigated using online database. Meta-analyses were conducted using RevMan v5.0 and STATA v12.0. RESULTS: Fourteen publications with 2951 cases were included. The incidence of high CD73 expression was 0.50 (95% CI: 0.36-0.63). Data from Oncomine validated that median CD73 expression level in tumor tissues was markedly higher than that in normal tissues in most kinds of cancers except cecum adenocarcinoma and ovarian cancer (P < 0.05). High CD73 expression was significantly correlated with shorter overall survival (OS) in various cancers (high risk [HR] = 1.48; P < 0.05). Subgroup analysis using online database demonstrated that high CD73 expression was significantly correlated with poor OS in breast (HR = 1.23; P < 0.05) and ovarian cancer (HR = 1.14; P < 0.05), but favorable OS in lung (HR = 0.80; P < 0.05) and gastric cancer (HR = 0.71; P < 0.05). High CD73 expression was dramatically associated with lymph node metastases (OR = 2.61; P = 0.05). CONCLUSION: High CD73 expression was significantly associated with lymph node metastases and a promising prognostic factor in different types of cancers.

Prognostic Value of Serum Lactate Dehydrogenase in Patients with Nasopharyngeal Carcinoma: a Meta-Analysis.

BACKGROUND: Serum-lactate dehydrogenase (S-LDH) is reported to be associated with poor survival in patients with nasopharyngeal carcinoma (NPC); however, the results are inconsistent. The aim of the study was to perform a meta-analysis to evaluate the prognostic value of S-LDH in patients with NPC. METHODS: PubMed and Web of Science were searched for relevant studies, and the fixed-effects model was employed to pool the hazard risks (HRs) from individual studies when no substantial heterogeneity was detected; otherwise, the random-effects model was used. Heterogeneity and publication bias were also analyzed. RESULTS: A total of 18 studies involving 13,789 patients were included in the meta-analysis, serum LDH level was associated with worse outcome in NPC patients. The combined HR for overall survival (OS) was 1.86 (95% confidence interval [CI]: 1.66 - 2.08; p < 0.01), and the pooled HRs for disease-free survival (DFS), distant metastasisfree survival (DMFS), and distant local relapse-free survival (LRFS) were 1.64 (95% CI: 1.45 - 1.86), 2.64 (95% CI: 2.15 - 3.25), and 2.59 (95% CI: 1.74 - 3.87), respectively. CONCLUSIONS: Our results suggest that higher serum LDH level is associated with worse survival in patients with NPC, which is helpful for a personalized treatment strategy for NPC patients.

Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured In Vitro of SCLC Patients.

PURPOSE: The prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs. METHODS: Based on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated. RESULTS: All of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease. CONCLUSION: The results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.

Characterization of PD-L1 protein expression and CD8+ tumor-infiltrating lymphocyte density, and their associations with clinical outcome in small-cell lung cancer.

BACKGROUND: This study aimed to characterize programmed death ligand-1 (PD-L1) expression and CD8+ tumor-infiltrating lymphocytes (TILs) density, and their impact on survival in patients with surgically resected small-cell lung cancer (SCLC). METHODS: Fifty-six patients with surgically resected SCLC were included. PD-L1 protein expression and CD8+ TILs were tested by immunohistochemistry. A meta-analysis of 15 articles with 1,505 patients that investigated the prevalence and prognostic significance of PD-L1 expression in SCLC was conducted. RESULTS: Twenty-two (39.3%) patients had positive PD-L1 protein expression and 42 (75.0%) had high CD8+ TILs density. PD-L1 expression level was not associated with CD8+ TILs density (P=0.528). No any association between clinicopathological features and PD-L1 expression level or CD8+ TILs density was observed. Positive PD-L1 expression [hazard ratio (HR) =0.374, P=0.002] and high CD8+ TILs density (HR =0.429, P=0.008) were independently associated with significantly longer overall survival (OS), which remain the statistical significance in multivariate analyses (P=0.007, P=0.002; respectively). Meta-analysis showed that the prevalence of positive PD-L1 expression was 0.35 [95% confidence interval (CI), 0.22-0.48] and positive PD-L1 expression was correlated with markedly longer OS (HR =0.61; 95% CI, 0.31-0.91) in patients with SCLC. CONCLUSIONS: The prevalence of PD-L1 expression in surgically resected SCLC is lower than that published for NSCLC. There was no association between PD-L1 expression or CD8+ TILs density and clinicopathological parameters. PD-L1 expression and CD8+ TILs density was independently correlated with better outcome in patients with SCLC.

The diagnostic value of circulating cell free DNA quantification in non-small cell lung cancer: A systematic review with meta-analysis.

OBJECTIVES: The aim of the current study was to assess the diagnostic value of circulating cell free DNA (cfDNA) quantification in discriminating non-small cell lung cancer (NSCLC) from healthy individuals. MATERIALS AND METHODS: An electronic search was conducted on PubMed, EMBASE, Web of Science, and Cochrane Library. Eligible studies regarding to examine the diagnostic value of cfDNA in the detection of NSCLC were extracted and analyzed. RESULTS: We identified 15 eligible studies with a total of 2125 patients. The pooled results for quantification of cfDNA in lung cancer screening in the included studies were as follows: sensitivity, 81% (95% confidence interval (CI), 76%-84%); specificity, 85% (95% CI, 77%-91%); diagnostic odds ratio, 23.87 (95% CI, 13.37-42.61); and areas under the summary receiver operating characteristic curves were 0.89 (95% CI, 0.86-0.92). Subgroup analyses according to the time of sample collection, sample materials, test method, reference gene and cutoff value did not improve sensitivity, but specificity could be significantly improved when we only included the studies using cfDNA sample before surgery or antitumor treatment and real-time PCR to detect cfDNA and human ß-actin as a reference gene. CONCLUSION: Quantification of cfDNA was a promising and effective biomarker for discriminating NSCLC from healthy individuals.