Many studies have investigated the diagnostic role of circulating microRNAs (miRNAs) in patients with lung cancer; however, the results still remain inconclusive. An updated system review and meta-analysis was necessary to give a comprehensive evaluation of diagnostic role of circulating miRNAs in lung cancer. Eligible studies were searched in electronical databases. The sensitivity and specificity were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The between-study heterogeneity was evaluated by Q test and I2 statistics. Subgroup analyses and meta-regression were further performed to explore the potential sources of heterogeneity. A total of 134 studies from 65 articles (6,919 patients with lung cancer and 7,064 controls) were included for analysis. Overall analysis showed that circulating miRNAs had a good diagnostic performance in lung cancers, with a sensitivity of 0.83, a specificity of 0.84, and an AUC of 0.90. Subgroup analysis suggested that combined miRNAs and Caucasian populations may yield relatively higher diagnostic performance. In addition, we found serum might serve as an ideal material to detecting miRNA as good diagnostic performance. We also found the diagnostic role of miRNAs in early stage lung cancer was still relatively high (the sensitivity, specificity and an AUC of stage I/II was 0.81, 0.82 and 0.88; and for stage I, it was 0.80, 0.81, and 0.88). We also identified a panel of miRNAs such as miR-21-5p, miR-223-3p, miR-155-5p and miR-126-3p might serve as potential biomarkers for lung cancer. As a result, circulating miRNAs, particularly the combination of multiple miRNAs, may serve as promising biomarkers for the diagnosis of lung cancer.

Published studies have investigated the prognostic role of cyclooxygenase-2 (COX-2) expression in patients with esophageal cancer (EC), but the result remains controversial. Thus, this meta-analysis was conducted to comprehensively evaluate the impact of COX-2 expression on the prognostic value in patients with EC. Relevant studies were identified from PubMed, EMBASE, and Web of Science databases. Studies that detected the COX-2 expression by immunohistochemistry and evaluated the relationship between COX-2 expression and overall survival (OS) or clinicopathological parameters were used in our analysis. The summary hazard ratios (HRs) or odds ratios were calculated to assess the risk or hazard association. A total of 25 studies, which included 2,465 patients, were included in our meta-analysis. Our analysis suggested that overexpression of COX-2 was associated with poor OS (HR =1.60, 95% CI =1.32–1.94, P<0.001). Subgroup analyses by race, percentage of high/positive COX-2 expression, histology type, treatment, and sample size all suggested significant association. Moreover, overexpression of COX-2 was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and TNM stage. This meta-analysis suggested that overexpression of COX-2 might serve as a prognostic biomarker for EC. Large well-designed prospective studies are needed to confirm our conclusion.

Objective It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype. Methods Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses. Results Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20–2.21) and OS (HR 1.53, 95% CI 1.19–1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45–2.85) and OS (HR 2.26, 95% CI 1.46–3.52) were also poor in the subgroup of patients with the presence of an MP component. Conclusions Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.

PurposeXuanwei City is located in late Permian coal-accumulating areas of the northeastern region of Yunnan Province. In China, morbidity and mortality from lung cancer are highest in Yunnan. Identifying useful circulating markers suitable for the diagnosis of lung cancer in this region is quite meaningful. In this study, we evaluated diagnostic roles of serum miR-9-5p, 21-5p, 223-3p, 135b-5p, 339-5p, and 501-5p in patients with non-small-cell lung cancer (NSCLC) in Yunnan. Moreover, we evaluated the diagnostic performance of several tumor markers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), and squamous cell carcinoma-related antigen (SCC).MethodsQuantitative real-time polymerase chain reaction detected six miRNAs in the serum of 104 NSCLC patients and 50 cancer-free controls. Other markers, including CEA, CYFRA21-1, and SCC, in serum were also measured. The diagnostic ability of miRNAs and tumor markers was evaluated by receiver operating characteristic (ROC) curve analysis. The diagnostic performance of these serum markers was also evaluated in Xuanwei and non-Xuanwei subjects, because the etiological and the epidemiological characteristics of lung cancer in Xuanwei were quite different from those in other regions.ResultsSerum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were upregulated in NSCLC patients, compared with cancer-free controls. No significant difference was found in miR-135b-5p, miR-339-5p, and miR-501-5p expression. The area under ROC curves (AUCs) of miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC were 0.706, 0.765, 0.744, 0.749, 0.735, and 0.616, respectively. When combined, miRNAs and tumor markers yielded the highest diagnostic power, with AUC of 0.886, sensitivity of 82.69%, and specificity of 88.00%. In Xuanwei subjects, miR-223-3p and CEA may be suitable biomarkers to distinguish NSCLC from cancer-free states with AUCs of 0.752 and 0.791, respectively. The diagnostic power of the combination of miRNAs and tumor markers was still the highest in both subgroups (region: Xuanwei and non-Xuanwei; stages: I–II and III–IV).ConclusionSerum miR-9-5p, miR-21-5p, miR-223-3p, CEA, CYFRA21-1, and SCC could be potential diagnostic biomarkers for NSCLC patients in Yunnan. miRNAs and tumor markers should be combined to diagnose NSCLC, as it showed better ability for screening patients with NSCLC.

MicroRNAs (miRNAs) have been proved to be related to the development and progression of lung cancer. However, the expression signatures of miRNAs in lung adenocarcinoma in Xuanwei are not yet clear. The current study aimed to identify the potential miRNA profiles in lung adenocarcinoma in Xuanwei by microarray. The miRNA profiles in 24 lung adenocarcinoma and paired non-tumor tissues in Xuanwei were ascertained by using the Exiqon miRCURY LNA microRNA Array (v.18.0). The results of the microarrays were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) detection. Bioinformatics analysis was used to carry out the functional annotations of differentially expressed miRNAs. One hundred fifty five differentially expressed (≥2-fold change) miRNAs were identified (65 upregulated and 90 downregulated). QRT-PCR was used to validate the top 4 most upregulated and downregulated miRNAs, and the results were generally consisted with microarray. Furthermore, the differentially expressed miRNAs were significantly enriched in numerous common pathways that were bound up with cancer. The pathways included focal adhesion and signaling pathways, such as cyclic guanosine monophosphate -protein kinase G (cGMP-PKG) signaling pathways, mitogen-activated protein kinase (MAPK) signaling pathway, and Hippo signaling pathway, etc. Our study identified the potential miRNA profiles in lung adenocarcinoma in Xuanwei by microarray. These miRNAs might be used as biomarkers for diagnosis and/or prognosis for lung cancer in Xuanwei and therefore warrant further investigation. Further study is needed to reveal the potential role of these miRNAs in the carcinogenesis of XuanWei Lung Cancer (XWLC).