miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer

Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan–Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC.

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B3GNT3 overexpression is associated with unfavourable survival in non-small cell lung cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2017-204860 ◽

2018 ◽

Vol 71 (7) ◽

pp. 642-647 ◽

Cited By ~ 4

Author(s):

Liuwei Gao ◽

Hua Zhang ◽

Bin Zhang ◽

Jinfang Zhu ◽

Chen Chen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Disease Free Survival ◽

Small Cell ◽

Clinicopathological Parameters ◽

Small Cell Lung ◽

Nsclc Tissue ◽

Clinical Prognosis ◽

Nsclc Patients

ObjectiveThe aim of this study was to evaluate the expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) in non-small cell lung cancer (NSCLC) patients and to investigate the relevance of B3GNT3 expression in tumour prognosis.MethodsIn this study, B3GNT3 expression was examined in five pairs of resectable NSCLC tissue by Western blot and in 42 pairs of resectable NSCLC tissue by quantitative real-time PCR (qRT-PCR). Immunohistochemistry and statistical analysis were performed to assess the relationship between B3GNT3 expression scores and clinicopathological parameters, as well as clinical prognosis in a retrospective cohort of 176 NSCLC patients.ResultsBoth B3GNT3 mRNA and protein expression levels were significantly higher in NSCLC tissue than in adjacent normal tissue. In the 176 NSCLC cases, a high B3GNT3 expression level was positively correlated with lymph node metastasis (P<0.001) and advanced TNM stage (P=0.043). Kaplan-Meier analysis indicated that patients with high B3GNT3 expression had significantly lower disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001) than those with low B3GNT3 expression. Moreover, in the multivariate analyses, B3GNT3 expression was an independent prognostic factor for DFS (HR 0.329, 95% CI 0.213 to 0.508, P<0.001) and OS (HR 0.383, 95% CI 0.249 to 0.588, P<0.001).ConclusionsOur study demonstrated that high expression of B3GNT3 was associated with unfavourable DFS and OS in NSCLC patients, suggesting that B3GNT3 might be a potential prognostic biomarker for NSCLC.

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Association between Circulating Inflammatory Proteins and Clinical Prognosis in Chinese Patients with EGFR Mutation–Positive Non–Small Cell Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.05.027 ◽

2019 ◽

Vol 14 (10) ◽

pp. e222-e224

Author(s):

Rui Guan ◽

Anqi Lin ◽

Peng Luo ◽

Jian Zhang

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Chinese Patients ◽

Small Cell Lung ◽

Clinical Prognosis ◽

Inflammatory Proteins

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High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1

Oncotarget ◽

10.18632/oncotarget.17650 ◽

2017 ◽

Vol 8 (29) ◽

pp. 47389-47399 ◽

Cited By ~ 18

Author(s):

Zhu Liang ◽

Rui Kong ◽

Zhan He ◽

Li-Yao Lin ◽

Shan-Shan Qin ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

High Expression ◽

Small Cell Lung ◽

Clinical Prognosis

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Extracellular Vesicles in Non-Small-Cell Lung Cancer: Functional Role and Involvement in Resistance to Targeted Treatment and Immunotherapy

Cancers ◽

10.3390/cancers12010040 ◽

2019 ◽

Vol 12 (1) ◽

pp. 40 ◽

Cited By ~ 3

Author(s):

Luigi Pasini ◽

Paola Ulivi

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Progression ◽

Cell Lung Cancer ◽

Resistance Mechanisms ◽

Small Cell ◽

Biologically Active ◽

Small Cell Lung ◽

Clinical Prognosis ◽

Monitoring Therapy

Targeted and immunological therapies have become the gold standard for a large portion of non-small cell lung cancer (NSCLC) patients by improving significantly clinical prognosis. However, resistance mechanisms inevitably develop after a first response, and almost all patients undergo progression. The knowledge of such a resistance mechanism is crucial to improving the efficacy of therapies. So far, monitoring therapy responses through liquid biopsy has been carried out mainly in terms of circulating tumor (ctDNA) analysis. However, other particles of tumor origin, such as extracellular vehicles (EVs) represent an emerging tool for the studying and monitoring of resistance mechanisms. EVs are now considered to be ubiquitous mediators of cell-to-cell communication, allowing cells to exchange biologically active cargoes that vary in response to the microenvironment and include proteins, metabolites, RNA species, and nucleic acids. Novel findings on the biogenesis and fate of these vesicles reveal their fundamental role in cancer progression, with foreseeable and not-far-to-come clinical applications in NSCLC.

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The association between IDO activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic body radiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21054 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21054-e21054

Author(s):

Yaoyao Zhu ◽

Min Hu ◽

Qinghua Xu ◽

Yaping Xu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Cox Proportional Hazards Model ◽

Rank Test ◽

Small Cell Lung ◽

Clinical Prognosis ◽

Immune Activity ◽

Before And After

e21054 Background: Immunity affects the efficacy of radiotherapy of lung cancer patients. Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that converts tryptophan (T) into heparin (K), which can promote immune suppression and assist tumor cells in immune evasion. The purpose of this study was to quantitatively analyze the immune activity of IDO in serum before and after SBRT, and to explore the changes in immune activity of IDO mediated by SBRT and its relationship with patient's survival. Methods: High-performance liquid chromatography and mass spectrometry were used to determine serum K and T in 30 patients with early non-small cell lung cancer before and after SBRT treatment. K: T stands for IDO activity. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Cox proportional hazards model was used for univariate and multivariate analyses. Results: The median follow-up time was 37.4 months. The median PFS was 37.5 (95% CI, 31.0-44.0) months. The median survival was not reached. In all patients, lower post/pre kynurenine ratio correlated significantly with better PFS (HR = 0.31, 95% CI = 0.11-0.90, P = 0.032). The lower K: T ratio at post-RT received longer OS (HR = 0.27, 95% CI = 0.079-0.95, P = 0.042). In multivariate analysis, smoking < 30 packs / year (P = 0.030), higher BED (P < 0.001), and lower post/pre kynurenine (P = 0.043) were associated with better PFS. Lower K: T ratio post-RT (P = 0.040) and higher BED (P < 0.001) were significantly associated with better OS. Conclusions: SBRT could alter IDO-mediated antitumor immune activity. The lower level of post/pre kynurenine ratio was significantly related with better PFS. The lower K: T ratio at post-RT was related with better OS. This study shows that IDO is a potentially valuable biomarker for monitoring the immune status and predicting survival in early NSCLC patients after SBRT.

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