BackgroundThe subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed.ResultsBased on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA–based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer.MethodsTwo hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system.ConclusionsTaken together, these findings suggest that the 3 miRNA–based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma.

Due to the lack of an accurate preoperative diagnostic method of central lymph node metastasis (CLNM) of papillary thyroid cancer (PTC), the prophylaxis of central lymph node dissection remains controversial. The present study investigated the clinicopathological features of PTC patients and the risk factors of CLNM. The clinicopathological features of PTC patients with respect to sex, age, initial symptoms, observation, tumor diameter, multifocality, extrathyroidal invasion, and pathological data combined with other thyroid diseases, were analyzed retrospectively. The risk factors of CLNM were analyzed by Chi-squared test and multivariate logistic regression model. The CLNM rate of PTC was 40.6% (1331/3273). On average, 7.0 (4.0, 12.0) central lymph nodes were dissected, and 3.70 (±3.8) lymph nodes were proved to be metastatic. Univariate analysis showed that sex (P < .001), age (P < .001), tumor diameter (P < .001), extrathyroid invasion (P < .001), multifocality (P = .001), concurrent nodular goiter (P < .001), initial symptoms (P < .001), and observation or not (P < .001) were related to CLNM. The observation time was neither related to CLNM (P = .469) nor extrathyroidal invasion (P = .137). Tumors localized in the lower part of the thyroid were the risk factors for CLNM (P < .001) while multifocality was unrelated (P = .68). The metastasis rate of bilateral multiple regions > unilateral multiple regions > single region (P = .003). Multivariate logistic regression analysis showed that sex, age, tumor diameter, extrathyroidal invasion, and observation were independent risk factors of CLNM. Male, younger age, large tumor size, and extrathyroidal invasion were independent risk factors for CLNM. CLNM was related to multiple regions occupied by tumors in the thyroid but unrelated to multifocality. The tumor occupying a single region and localized in the lower part of thyroid could be used as a predictive factor for CLNM. For tumors that could not be diagnosed as benign or malignant, observation may be an option, since no evidence of disease progression was presented during observation.

More and more studies indicate the relevance of miRNAs in inducing certain drug resistance. Our study aimed to investigate whether microRNA‐130b‐3p (miR‐130b) mediates the chemoresistance as well as proliferation of lung cancer (LC) cells. MTS assay and apoptosis analysis were conducted to determine cell proliferation and apoptosis, respectively. Binding sites were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT‐PCR and immunoblot, respectively. Mouse xenograft model was used to evaluate the role of miR‐130b in cisplatin resistance in vivo. The rising level of miR‐130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. We identified PTEN as miR‐130b's major target and inversely correlated with miR‐130b expression in LC. Moreover, excessive miR‐130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. Suppression of miR‐130b enhanced drug cytotoxicity and reduced proliferation of A549/CR cells both internally and externally. Particularly, miR‐130b mediated Wnt/β‐catenin signalling pathway activities, chemoresistance and proliferation in LC cell, which was partially blocked following knockdown of PTEN. These findings suggest that miR‐130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/β‐catenin pathway. The rising level of miR‐130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. Moreover, excessive miR‐130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. These findings suggest that miR‐130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/β‐catenin pathway.

The SARI (suppressor of AP-1, regulated by IFN) gene, which is also called BATF2, is associated with the risk of several kinds of cancer, and loss of SARI expression is frequently detected in aggressive and metastatic cancer. However, the functional role of SARI in lung adenocarcinoma remains unknown. We have shown that loss of SARI expression initiates epithelial-mesenchymal transition (EMT), which is visualized by repression of E-cadherin and up-regulation of vimentin in lung adenocarcinoma cell lines and in clinical lung adenocarcinoma specimens. Using a human lung xenograft-mouse model, we observed that knocking down endogenous SARI in human carcinoma cells leads to the development of multiple lymph node metastases. Moreover, we showed that SARI functions as a critical protein in regulating EMT by modulating the (GSK)-3β-β-catenin signaling pathway. These results demonstrate the mechanism of SARI function in EMT and suggest that assessment of SARI may serve as a prognostic biomarker and potential therapeutic target for lung adenocarcinoma metastasis.

BackgroundSpecific biomarkers for early detection and outcome prediction of lung squamous cell carcinoma (LSCC) are still lacking. This study assessed the differentially expressed miRNAs as potential biomarkers for early stage LSCC.ResultsBase on the results of multi-phase study, we found that miR-324-3p was significantly up-regulated, whereas mir-1285 was significantly down-regulated in plasma of stage I LSCC patients compared to healthy controls. ROC analysis showed that AUC of miR-324-3p and miR-1285 were 0.79 and 0.85, respectively. The combination of these two miRNAs could further improve the diagnostic accuracy (AUC = 0.89). The multivariate analysis revealed that plasma miR-324-3p level was an independent prognostic predictor for early stage LSCC.Methods395 patients and 195 healthy controls were enrolled in this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. We also evaluated the association of candidate miRNAs with overall survival of early stage LSCC patients. Finally, the target genes of the candidate miRNAs were analyzed using public available databases and bioinformatics methods.ConclusionsThe current study suggests that plasma miR-324-3p and miR-1285 levels could serve as LSCC early detection markers while miR-324-3p may serve as a prognostic marker for LSCC patients.

Medical staffs lack the basic knowledge and harbor misconceptions about the clinical use of morphine for cancer pain treatment. Creating training opportunities for medical staffs is necessary to increase their awareness and knowledge of effective cancer pain management.

Expansion of CD4+CD25+ regulatory T cells (Tregs) in tumor microenvironment was one of the mechanisms by which cancer cells escaped host defense. Thymic stromal lymphopoietin (TSLP) contributes to the generation of natural Tregs in thymus. Therefore, the purpose of this report was to investigate the role of TSLP in the increasing prevalence of Tregs in lung cancer microenvironment. The expression ratio of TSLP protein in tumor tissues was significantly increased compared with that in benign lesion and non-cancer lung tissue. The prevalence of Tregs in tumor microenvironment was correlated with the expression of TSLP in lung cancer. Dendritic cells (DCs) were induced from peripheral blood mononuclear cells (PBMCs) collected from lung cancer patients and left unstimulated (imDCs) or exposed to hTSLP (TSLP-DCs) or LPS (LPS-DCs). TSLP-DCs expressed intermediate levels of CD83 and high levels of CD86, CD11C, and HLA-DR, which showed a characteristic of less mature DCs. TSLP-DCs secreted low levels of IL-6, IL-12, IL-10, TNF-α and IFN-γ, and high levels of TGF-β and MDC. The percentage of Tregs in CD4+CD25- T cells cocultured with TSLP-DCs group was statistically higher than that of LPS-DCs and imDCs. Transwell assays showed that TSLP-DCs exhibited increased ability to attract the migration of CD4+CD25- Tregs, when compared with imDCs. These results indicated that TSLP proteins were expressed in lung tumor tissue and correlated with the prevalence of Tregs. TSLP-DCs could induce CD4+CD25- T cells to differentiate into CD4+CD25+foxp3+ T cells and the migration of CD4+CD25+ T cells.

Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.