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Background: Effective biomarkers for early diagnosis of lung cancer are needed. Previous studies have indicated positive associations between abnormal circulating cytokines and the etiology of lung cancer. Methods: Blood samples were obtained from 286 patients with pretreatment lung cancer and 80 healthy volunteers. Circulating cytokine levels were detected with a Luminex assay and enzyme-linked immunosorbent assay (ELISA). Urine samples were obtained from 284 patients and 122 healthy volunteers. CXC chemokine ligand 14 (CXCL14) expression in tumors and nontumor regions of lung tissues from 133 lung cancer cases was detected by immunohistochemical (IHC) staining and immunofluorescence (IF) staining of formalin fixed paraffin-embedded (FFPE) tissues. Results: Compared with healthy volunteers, a 65.7-fold increase was observed in the level of CXCL14 in the plasma of lung cancer patients, and a 1.7-fold increase was observed in the level of CXCL14 in the urine of lung cancer patients, achieving a 0.9464 AUC (area under the curve) value and a 0.6476 AUC value for differentiating between lung cancer patients and healthy volunteers, respectively. Stromal CXCL14 expression was significantly associated with advanced pathologic stage (P <0.001), pathologic N stage (P <0.001), and recurrence and metastasis (P =0.014). Moreover, multivariate analysis suggested stromal CXCL14 expression as an independent predictor of DFS and OS. Conclusions: Our study demonstrates that CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer. Impact: CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the relation between the metastatic lymph node ratio (LNR) and the prognosis of non-small-cell lung cancer (NSCLC). Methods: A total of 301 patients with N1 or N2 NSCLC who underwent complete pulmonary resection were analyzed retrospectively. The correlations between the LNR and clinical and pathologic data were analyzed using χ test analysis. The prognostic value of the LNR was calculated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The risk groups were classified by a combination of the LNR and pN stage. Results: The LNR was correlated with age, smoking status, pathologic type, subcarinal lymph node, clinical staging, N stage ( P < 0.05), and the number of positive lymph nodes and positive lymph node stations ( P < 0.0001). In the univariate analysis, the LNR played an important role in predicting overall survival (OS) ( P < 0.0001) and disease-free survival ( P < 0.0001) by Kaplan-Meier survival analysis. In the multivariate analysis, high LNR (>18%) was an independent poor prognostic factor for OS [hazard ratio (HR) 2.5034, 95% confidence interval (CI) 1.6096-3.8933, P < 0.0001] and DFS (HR 1.9023, 95% CI 1.2465-2.9031, P = 0.0031). Stratification into high-, medium-, and low-risk groups-based on high-risk factors (LNR > 18%, N2) intermediate-risk factors (LNR > 18%, N1 or LNR < 18%, N2), and low-risk factors (LNR < 18%, N1)-could efficiently predicted outcomes ( P < 0.0001) of patients with lymph node-positive NSCLC. Conclusions: The combination of the LNR and pN status provides a valuable help with prognosis. However, these results must be evaluated further in a large prospective randomized clinical trial. [ABSTRACT FROM AUTHOR]

First-generation EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib have significant activity in NSCLC patients with activating EGFR mutations. However, EGFR-TKI resistance inevitably occurs after approximately 12 months of treatment. Acquired mechanisms of resistance, other than secondary mutations in EGFR (T790 M) which account for 50-60%, are less well understood. Here, we identified lncRNA H19 as a significantly downregulated lncRNA in vitro models and clinical specimens with acquired EGFR-TKI resistance, H19 knockdown or overexpression conferred resistance or sensitivity, respectively, both in vitro and in vivo models. H19 downregulation contributed to erlotinib resistance through interaction and upregulation of PKM2, which enhanced the phosphorylation of AKT. AKT inhibitors restored the sensitivity of erlotinib-resistant cells to erlotinib. In EGFR-mutant patients treated with EGFR-TKIs, low H19 levels were associated with a shorter progression-free survival (PFS) (P = 0.021). These findings revealed a novel mechanism of low-level H19 in the regulation of erlotinib resistance in EGFR-mutant lung cancers. Combination of AKT inhibitors and EGFR-TKIs could be a rational therapeutic approach for some subgroups of EGFR-mutant lung cancer patients. [ABSTRACT FROM AUTHOR]