Diagnosis and treatment at an early stage may improve survival of non-small-cell lung cancer (NSCLC). Previous studies have found that long noncoding RNA growth arrestspecific transcript 5 (GAS5) is essential to cancer progression. However, the expression and diagnostic value of GAS5 in exosomes (Exo-GAS5) remain unclear. One hundred and four participants were enrolled, including subjects with NSCLC (n = 64) and healthy subjects (n = 40). The total Exosome Isolation Kit was applied to isolate exosomes from serum. Total RNA was extracted and the AS5 expression was analyzed using quantitative reverse transcription polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic value of Exo-GAS5 in NSCLC. Our data indicated that the Exo-GAS5 was downregulated in patients with NSCLC compared with healthy controls (p < 0.001). Furthermore, patients with NSCLC with larger tumor size (p = 0.025) and advanced TNM (T: extent of the primary tumor; N: lymph node involvement; M: metastatic disease) classification (p = 0.047) showed lower Exo-GAS5 expression. ROC curve analysis using Exo-GAS5 combined with carcinoembryonic antigen showed an area under curve (AUC) of 0.929. Exo-GAS5 could be used to distinguish patients with Stage I NSCLC with an AUC of 0.822. In conclusion, Exo-GAS5 may function as an ideal noninvasive serum-based marker for identifying patients with early NSCLC.
K E Y W O R D Sbiomarker, exosomes, GAS5, NSCLC
Several studies have shown the tumorigenesis role of transcriptional enhancer associate domain (TEAD) proteins; here, we initially explored expression, function and signalling mechanisms of TEAD4 in lung adenocarcinoma (LAD). Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour‐promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial‐mesenchymal transition (EMT) markers such as E‐cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4‐targeted microRNA, namely miR6839‐3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839‐3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839‐3p mimics as a promising therapeutic direction.
Young patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
The current study was to perform qualitative comparison of photodynamic therapy (PDT), based on previously published articles on spinal disease distribution status before and after treatment. Spinal metastasis, the migration of primary cancer cells and establishment of secondary tumors in the spine. We electronically searched CENTRAL (The Cochrane Library 2012), MEDLINE, EMBASE, CINAHL and AMED (from their beginning to December 31, 2012) to identify published studies assessing the effectiveness of PDT in spinal metastases. Our inclusion criteria resulted in only 4 articles, all in mice models. Due to study limitations and sparse data, the quality of evidence for all outcomes was low. Our analyses shows that effects on stereological and mechanical properties observed at the 1-week time point post-PDT are maintained at a longer 6-week time point, with combined PDT þ bisphosphonate treatment being the most beneficial in terms of bone enhancement. Additionally, the combination of PDT þ radiation therapy also demonstrated significant increases in stereological parameters, suggesting that previous radiation therapy treatment does not preclude the boneenhancing effects of PDT and in fact may be synergistic in the longer term. The boneenhancing effects of PDT in combination with conventional treatments, and its ability to destroy metastatic human breast cancer cells within bone, present PDT as an attractive novel treatment for spinal metastasis. The positive results from these preclinical studies might motivate future clinical translation of PDT for spinal metastasis.
tRNA-derived small RNAs (also known as tsRNAs) are novel kinds of non-coding RNAs. Although tsRNAs are aberrantly expressed in different tumor types, there is scanty of research investigating their expression profiling and functions in pulmonary adenocarcinoma (PADC). We identified the expression of AS-tDR-007872 in 30 non-small-cell lung carcinoma (NSCLC) patients’ carcinoma tissues and conducted biological function evaluation. We also test the expression levels of AS-tDR-007872 in plasma samples obtained from 35 healthy people and 79 NSCLC cases. The results identified downregulated AS-tDR-007872 in both cancer tissues and plasma samples versus adjacent normal counterparts (
p
<
0.05
) and healthy controls (
p
<
0.001
). The area under the curve of AS-tDR-007872 was identified by receiver operating characteristic curve analysis to be 0.756 (95% CI, 0.663-0.849;
p
<
0.001
). Furthermore, overexpression of AS-tDR-007872 in vitro inhibited tumor cell proliferation, invasion, and migration and promoted apoptosis. The knockdown of AS-tDR-007872 showed the opposite results. Meanwhile, we found significantly downregulated BCL2L11 after overexpressing AS-tDR-007872. From the above, our research suggests that AS-tDR-007872 can be a tumor suppressor and a promising biomarker for diagnosing lung cancer.
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