Recent diagnostic procedure advances have considerably improved early lung cancer detection. However, the invasive, unpleasant, and inconvenient nature of current diagnostic procedures limits their application. There is a great need for novel noninvasive biomarkers for early lung cancer diagnosis. In the present study, we aimed to determine whether microRNA (miRNA) blood signatures are suitable for early detection of lung cancer. Using quantitative reverse transcriptase PCR analysis, we first selected and identified three aberrant plasma expression miRNAs (miR-21, miR-145, and miR-155) in a training set of 62 patients and 60 healthy smokers to define a panel that had high diagnostic efficiency for lung cancer. Then, we validated the detective ability of this miRNA panel in a testing set of 34 malignant tumor patients, 30 patients with benign pulmonary nodules and 32 healthy smokers. In the training set, miR-21 and miR-155 showed higher plasma expression levels, whereas miR-145 showed a lower expression level in patients with malignant cancer, compared with healthy controls (P ≤ 0.001). The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.847, which helped distinguish lung cancer from healthy smokers with 69.4% sensitivity and 78.3% specificity. A logistic regression model with the best prediction was constructed on the basis of miR-21, miR-145, and miR-155. Validation of the miRNA panel in the testing set confirmed their diagnostic value, which yields a significant improvement over any single one. Plasma miR-21, miR-145, and miR-155 have strong potential as novel noninvasive biomarkers for early detection of lung cancer.
BackgroundThe antisense of the OIP5‐AS1 gene is a long non‐coding RNA (lncRNA) that is reported to be upregulated and promotes cell proliferation in multiple human cancers; however, its function in lung cancer is unknown. We investigated the regulatory function and underlying mechanisms of OIP5‐AS1 in lung cancer.MethodsOIP5‐AS1 and microRNA (miR)‐378a‐3p expression were assayed by quantitative real‐time PCR, and proliferation‐related protein expression was measured by Western blotting. Cell viability was detected using methyl thiazolyl tetrazolium assay. Luciferase reporter assay and RNA immunoprecipitation were used to detect the direct regulation of miR‐378a‐3p by OIP5‐AS1. Nude mice were used to test the function of OIP5‐AS1 in vivo.ResultsOIP5‐AS1 was highly expressed in lung cancer tissues and was correlated with tumor size and tumor growth speed. OIP5‐AS1 overexpression increased lung cancer cell proliferation in vitro. Further investigation revealed that OIP5‐AS1 functions as a competing endogenous RNA of miR‐378a‐3p. MiR‐378a‐3p overexpression inhibited cell proliferation and caused proliferation‐associated proteins CDK4 and CDK6 to decrease in A549 cells. Overexpression of wild type OIP5‐AS1 led to strong CDK4 and CDK6 expression; however, these two proteins did not change when mutated OIP5‐AS1 was upregulated. Finally, in vivo assay showed that the speed of tumor growth was increased and decreased when OIP5‐AS1 was upregulated and downregulated, respectively.ConclusionOur results revealed that OIP5‐AS1 acts as a growth‐promoting lncRNA in lung cancer by suppressing miR‐378a‐3p function. OIP5‐AS1 and miR‐378a‐3p interaction may provide a potential target for lung cancer treatment.
Background: Circular RNAs (circRNAs) belong to a new type of endogenous non-coding RNA and plays a key role in carcinogenesis. Circ-ZKSCAN1 (hsa_circ_0001727) has been proven to be a tumor-dependent circRNA. However, its role in non-small cell lung cancer (NSCLC) has been underreported. Methods:The expression patterns of circ-ZKSCAN1 were determined using qRT-PCR in NSCLC samples and cell lines. Cell proliferation was examined utilizing the CCK-8 assay. Cell migration and invasion were evaluated using the Transwell assay. The combination of circ-ZKSCAN1 and miR-330-5p in NSCLC cells was analyzed by RNA pull-down and luciferase reporter assay. We used the bioinformatics software circbank, CircInteractome, TargetScan and Miranda to predict circRNA-miRNA and miRNA-mRNA interactions.Results: Our results showed that circ-ZKSCAN1 was significantly up-regulated in NSCLC, closely related to malignant characteristics and poor prognosis, and clinically related to tumor size and clinical stage.Subsequent experiments showed that circ-ZKSCAN1 could inhibit the growth of NSCLC cells in vitro and in vivo. Importantly, circ-ZKSCAN1 can act as a sponge of carcinogenic miR-330-5p to increase the expression of FAM83A, resulting in the inhibition of MAPK signal transduction pathway, thus promoting the progress of NSCLC. Interestingly, the increase in FAM83A expression caused by circ-ZKSCAN1 overexpression could in turn promote the expression of circ-ZKSCAN1.Conclusions: Circ-ZKSCAN1 is a key positive regulator of NSCLC, and clarifies the potential molecular mechanism of the new circ-ZKSCAN1/miR-330-5p/FAM83A feedback loop in promoting the progress of NSCLC.
Lung cancer has been identified as one of the most prevalent and deadly tumors worldwide. In recent years, lncRNAs have been demonstrated to play a significant role in the development of lung cancer. Specifically, lncRNAs act as a regulator of cancer-critical genes, and they regulate the biological behavior of tumors at the transcriptional and posttranscriptional levels. Recent studies have shown that lncRNAs possess great potential in the treatment of non-small cell lung cancer patients because of their roles in diverse cellular processes, such as proliferation, metastasis, stem cell maintenance, and epithelial to mesenchymal transition, and they serve as signaling biomarkers. Compared to other invasive diagnostic methods, detection of lncRNAs may become a very useful noninvasive methodology. Moreover, lncRNAs can serve as potential therapeutic targets in non-small cell lung cancer due to their roles in regulating many signaling pathways associated with lung carcinoma. In this review, we discuss the roles and expression profile of lncRNAs. We also discuss the promising application of lncRNAs as predictors of clinical diagnosis, prognosis, and as potential therapeutic targets, aiming to demonstrate their practical value for clinical treatment.
VATS resection and reconstruction of the carina or trachea are feasible, and these procedures can be safely performed using the techniques described. We believe, with the accumulation of VATS experience, these procedures could be adopted as routine approaches in tracheal surgery.
BackgroundLung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. The main obstacle to early diagnosis or monitoring of patients at high risk of poor survival has been the lack of essential predictive biomarkers.MethodsRNA-sequencing was performed on LUAD affected tissue and paired adjacent to noncancerous tissue samples and Gene Expression Omnibus dataset GSE19188 and GSE33532 were used to obtain an intersection of differential expressed genes and construct a protein–protein interaction network to get hub genes. Then corresponding overall survival information of two cohorts of LUAD patients from our hospital and The Cancer Genome Atlas project-LUAD were included in the present study. An analysis of the Kyoto Encyclopedia of Genes and Genomes database and Gene Ontology were carried out to study the signature mechanism.ResultsIn our study, we identified eight candidate genes (DLGAP5, KIF11, RAD51AP1, CCNB1, AURKA, CDC6, OIP5 and NCAPG) closely related to survival in LUAD. A linear prognostic model of the eight genes was constructed and weighted by the regression coefficient (β) from the multivariate Cox regression analysis of The Cancer Genome Atlas-LUAD cohort to divide patients into low- and high-risk groups. The prognostic ability of the signature was validated in LUAD patients at our hospital. Patients assigned to the high-risk group exhibited poor overall survival compared to patients in the low-risk group. Finally, functional enrichment analysis showed that cell division played a vital role in the development of LUAD.ConclusionThe study identified an mRNA signature including eight genes, which may serve as a potential prognostic marker of LUAD.
Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.
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