scholarly journals Elevated Exosome-derived Mirnas Predict Osimertinib Resistance in Non-small Cell Lung Cancer

2020 ◽  
Author(s):  
Xinying Li ◽  
Cen Chen ◽  
Zimu Wang ◽  
Jiaxin Liu ◽  
Wei Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Serum Exosomes

Abstract Background: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated with the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. In recent years, many studies have been focusing on the ability of exosomal miRNAs secreted by tumor cells to transmit resistance information. However, the mechanism of exosome-derived miRNAs in osimertinib resistance remains unexplored.Methods: We extracted and sequenced exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975. The results were compared with plasma exosome sequencing before and after the appearance of drug resistance in three NSCLC clinical patients treated with oral osimertinib. Exosome-derived miRNAs that had significantly increased expression levels after osimertinib resistance were screened for expanded validation in other 64 NSCLC patients.Results: Cluster analysis of the target genes revealed that exosomal miRNAs participate in osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality and PI3K pathway activation). Exosome-derived miR-184 (p = 0.0325) and miR-3913-5p (p = 0.0169) expression levels increased significantly after the onset of osimertinib resistance. Exosomal miR-184 was correlated with lactate dehydrogenase levels (p = 0.018). Exosomal miR-3913-5p was associated with TNM stage (p = 0.045), platelet count (p = 0.024), tumor marker carcinoembryonic antigen (p = 0.045), and distant metastases (p = 0.049), especially bone metastasis (p = 0.03). In the subgroup of patients with EGFR exon 21 L858R point mutation, miR-184 (p = 0.0104) and miR-3913-5p (p = 0.0085) derived from serum exosomes had both significantly increased expression levels. In the subgroup of T790M-positive patients, miR-3913-5p derived from serum exosomes may also be a good indicator of osimertinib resistance (p = 0.013).Conclusions: The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of NSCLC patients could be used as biomarkers to indicate osimertinib resistance.

scholarly journals Elevated exosome-derived miRNAs predict osimertinib resistance in non-small cell lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinying Li ◽  
Cen Chen ◽  
Zimu Wang ◽  
Jiaxin Liu ◽  
Wei Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Exosomal Mirnas ◽  
Nsclc Patients

Abstract Background Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated with the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. Recently, the drug resistance information transmitted by exosomal miRNAs has attracted much attention. However, the mechanism of exosome-derived miRNAs in osimertinib resistance remains unexplored. Methods We extracted and sequenced exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975. The results were compared with plasma exosome sequencing before and after the appearance of drug resistance in three NSCLC clinical patients treated with oral osimertinib. Exosome-derived miRNAs that had significantly increased expression levels after osimertinib resistance were screened for expanded validation in other 64 NSCLC patients. Results Cluster analysis of the target genes revealed that exosomal miRNAs participate in osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality and PI3K pathway activation). Exosome-derived miR-184 and miR-3913-5p expression levels increased significantly after the onset of osimertinib resistance. Exosomal miR-3913-5p was associated with TNM stage, platelet count, tumor marker carcinoembryonic antigen, and distant metastases. In patients with EGFR exon 21 L858R mutation, the increased expression levels of miR-184 and miR-3913-5p derived from serum exosomes indicated osimertinib resistance. Similarly, for T790M-positive patients, the level of exosome-derived miR-3913-5p can be used as a predictive marker for osimertinib resistance. Conclusions The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of NSCLC patients could be used as biomarkers to indicate osimertinib resistance. Graphic Abstract

scholarly journals Small cell lung cancer transformation during antitumor therapies: A systematic review

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1160-1167
Author(s):  
Xing Chai ◽  
Xinru Zhang ◽  
Wenqian Li ◽  
Jin Chai
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Histological Transformation ◽  
Nsclc Patients

Abstract Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major histological categories of lung cancers. Drug resistance is a great challenge for cancer treatment, and histological transformation from NSCLC to SCLC is one of the mechanisms underlying drug resistance in NSCLC patients. SCLC-transformed patients show combined characteristics of NSCLC and SCLC; however, they lack timely diagnoses and effective treatment strategies. Thus, we reviewed the clinical characteristics of SCLC transformation patients with a literature search to enhance clinical consciousness, diagnosis, and personalized treatment for patients with it.

Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23035-e23035 ◽  
Author(s):  
Marco Giallombardo ◽  
Jorge Jorge Chacartegui ◽  
Pablo Reclusa ◽  
Jan P. Van Meerbeeck ◽  
Riccardo Alessandro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Egfr Mutated

scholarly journals High expression of Aurora-B is correlated with poor prognosis and drug resistance in non-small cell lung cancer

2018 ◽  
Vol 33 (2) ◽  
pp. 215-221 ◽  
Author(s):  
JingJing Yu ◽  
Jing Zhou ◽  
Fei Xu ◽  
Wei Bai ◽  
Wei Zhang
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Poor Prognosis ◽  
Drug Response ◽  
Small Cell ◽  
Aurora B ◽  
Small Cell Lung ◽  
Nsclc Patients

Objective: Aurora kinase B (Aurora-B) is a crucial regulator of accurate mitosis. Abnormal Aurora-B expression is associated with aneuploidy and has been implicated in the pathogenesis and drug resistance in a variety of human cancers. However, little evidence is available regarding the role of Aurora-B in regulating drug response in non-small cell lung cancer (NSCLC), which is the most common type of lung cancer, and is characterized with poor prognosis and high mortality. Method: In the current study, we investigated the association of Aurora-B with the prognosis of NSCLC patients, and we also used the latest CRISPR/Cas9 system to explore the regulatory role of Aurora-B in NSCLC cells developing resistance to cisplatin (CDDP) and paclitaxel. Results: We found that Aurora-B was correlated with significantly reduced overall survival and disease-free survival in NSCLC patients. Aurora-B overexpression was also observed in NSCLC cells developing impaired response to both CDDP and paclitaxel. Moreover, we found, for the first time, that Aurora-B may impair NSCLC drug response by disturbing cell proliferation and inhibiting p53-related DNA damage response and apoptotic pathway, while the knockout of Aurora-B resensitized NSCLC cells to chemo drugs by ensuring correct chromosome segregation and restoring p53 expression. Conclusions: Our results demonstrated the association of Aurora-B with chemoresistance in NSCLC, which may finally contribute to the poor prognosis of NSCLC patients. We also suggested Aurora-B as a promising therapeutic target in NSCLC treatment.

Exosomal microRNAs as potential biomarkers for osimertinib resistance of non-small cell lung cancer patients

2021 ◽  
pp. 1-14
Author(s):  
Keatdamrong Janpipatkul ◽  
Narumol Trachu ◽  
Piyakarn Watcharenwong ◽  
Wittaya Panvongsa ◽  
Wittawin Worakitchanon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Molecular Biomarkers ◽  
Small Cell Lung ◽  
Clinical Prognosis ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Exosomal Mirna

BACKGROUND: Osimertinib is an epidermal growth factor receptor-tyrosine kinase inhibitor that specifically targets the T790M mutation in cancer.Unfortunately, most non-small cell lung cancer (NSCLC) patients develop osimertinib resistance. Currently, the molecular biomarkers for monitoring osimertinib resistance are not available. OBJECTIVE: This study aimed to examine the profile of exosomal miRNA in the plasma of osimertinib-resistant NSCLC patients. METHODS: Plasma exosomal miRNA profiles of 8 NSCLC patients were analyzed by next-generation sequencing at osimertinib-sensitive and osimertinib-resistance stage.The expression of dysregulated exosomal miRNAs was validated and confirmed in another cohort of 19 NSCLC patients by qPCR The relationship between exosomal miRNA upregulation and clinical prognosis, survival analysis was evaluated by Kaplan-Meier curves. RESULTS: In osimertinib-resistant NSCLC patients, 10 exosomal miRNAs were significantly dysregulated compared to baseline. Upregulation of all 10 candidate exosomal miRNAs tended to correlate with increased latency to treatment failure and improved overall survival. Among them, 4 exosomal miRNAs, miR-323-3p, miR-1468-3p, miR-5189-3p and miR-6513-5p were essentially upregulated and show the potential to be markers for the discrimination of osimertinib-resistance from osimertinib-sensitive NSCLC patients with high accuracy (p< 0.0001). CONCLUSIONS: Our results highlight the potential role of these exosomal miRNAs as molecular biomarkers for the detection of osimertinib resistance.

scholarly journals A Prognostic Role for Circulating microRNAs Involved in Macrophage Polarization in Advanced Non-Small Cell Lung Cancer

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1988
Author(s):  
Alexia Monastirioti ◽  
Chara Papadaki ◽  
Konstantinos Rounis ◽  
Despoina Kalapanida ◽  
Dimitrios Mavroudis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Macrophage Polarization ◽  
Small Cell ◽  
Small Cell Lung ◽  
Circulating Micrornas ◽  
Expression Levels ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

Circulating microRNAs (miRNAs) are key regulators of the crosstalk between tumor cells and immune response. In the present study, miRNAs (let-7c, miR-26a, miR-30d, miR-98, miR-195, miR-202) reported to be involved in the polarization of macrophages were examined for associations with the outcomes of non-small cell lung cancer (NSCLC) patients (N = 125) treated with first-line platinum-based chemotherapy. RT-qPCR was used to analyze miRNA expression levels in the plasma of patients prior to treatment. In our results, disease progression was correlated with high miR-202 expression (HR: 2.335; p = 0.040). Additionally, high miR-202 expression was characterized as an independent prognostic factor for shorter progression-free survival (PFS, HR: 1.564; p = 0.021) and overall survival (OS, HR: 1.558; p = 0.024). Moreover, high miR-202 independently predicted shorter OS (HR: 1.989; p = 0.008) in the non-squamous (non-SqCC) subgroup, and high miR-26a was correlated with shorter OS in the squamous (SqCC) subgroup (10.07 vs. 13.53 months, p = 0.033). The results of the present study propose that the expression levels of circulating miRNAs involved in macrophage polarization are correlated with survival measures in NSCLC patients, and their role as potential biomarkers merits further investigation.

scholarly journals LncRNA SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival

2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
feng wu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Poor Survival ◽  
Expression Levels ◽  
Tcga Dataset ◽  
Nsclc Patients

Abstract LncRNA SNHG10 has been characterized as an oncogenic lncRNA in liver cancer. By analyzing TCGA dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC), indicating its involvement in this disease. We then analyzed the role of SNHG10 in NSCLC. Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. The expression of SNHG10 and miR-21 in tissues were determined by RT-qPCR. Overexpression of SNHG10 or miR-21 in NSCLC cells was achieved and the interaction between them was evaluated. Cell proliferation was determined by CCK-8 assay. In this study we found that SNHG10 was downregulated in cancer tissues of NSCLC patients. High expression levels of SNHG10 predicted favorable survival of NSCLC patients. The expression levels of miR-21 were increased in NSCLC and inversely correlated with SNHG10. In NSCLC cells, overexpression of SNHG10 led to increased miR-21 gene methylation and decreased the expression levels of miR-21. In cell proliferation assay, overexpression of SNHG10 attenuated the enhancing effect of overexpression of miR-21 on cell proliferation. SNHG10 was downregulated in non-small cell lung cancer and predicted poor survival. It may downregulate miR-21 through methylation to suppress cancer cell proliferation.

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