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Role of cytokines in combinatorial immunotherapeutics of non-small cell lung cancer through systems perspective.

ABSTRACT: Lung cancer is the leading cause of deaths related to cancer and accounts for more than a million deaths per year. Various new strategies have been developed and adapted for treatment; still the survival for 5 years is just 16% in patients with non-small cell lung cancer (NSCLC). Most of these strategies to combat NSCLC whether it is a drug molecule or immunotherapy/vaccine candidate require a big cost and time. Integration of computational modeling with systems biology has opened new avenues for understanding complex cancer biology. Resolving the complex interactions of various pathways and their crosstalk leading to oncogenic changes could identify new therapeutic targets with lesser cost and time. Herein, this review provides an overview of various aspects of NSCLC along with available strategies for its cure concluding with our insight into how systems approach could serve as a therapeutic intervention dissecting the immunologic parameters and cross talk between various pathways involved.

SUBMITTER: Misra P

PROVIDER: S-EPMC6536974 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Role of cytokines in combinatorial immunotherapeutics of non-small cell lung cancer through systems perspective.

Misra Pragya P Singh Shailza S

Cancer medicine 20190417 5

Lung cancer is the leading cause of deaths related to cancer and accounts for more than a million deaths per year. Various new strategies have been developed and adapted for treatment; still the survival for 5 years is just 16% in patients with non-small cell lung cancer (NSCLC). Most of these strategies to combat NSCLC whether it is a drug molecule or immunotherapy/vaccine candidate require a big cost and time. Integration of computational modeling with systems biology has opened new avenues fo ...[more]

PMID: 30997737

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Project description:Tumor-promoting cytokines are a cause of tumor progression; therefore, identifying key regulatory microRNAs (miRNAs) for controlling their production is important. The aim of this study is to identify promising miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer (NSCLC). We identified circulating miRNAs from 16 published miRNA profiles. The selected miRNAs were validated in the serum of 32 NSCLC patients and compared with 33 patients with other lung diseases and 23 healthy persons using quantitative real-time PCR. The cytokine concentration was investigated using the enzyme-linked immunoassay in the same sample set, with clinical validation of the miRNAs. The correlation between miRNA expression and cytokine concentration was evaluated by Spearman's rank correlation. For consistent direction, one up-regulated miRNA (miR-145) was found in four studies, and seven miRNAs were reported in three studies. One miRNA (miR-20a) and four miRNAs (miR-25-3p, miR-223, let-7f, and miR-20b) were reported in six and five studies. However, their expression was inconsistent. In the clinical validation, serum miR-145 was significantly down-regulated, whereas serum miR-20a was significantly up-regulated in NSCLC, compared with controls. Regarding serum cytokine, all cytokines [vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and transforming growth factor β (TGF-β)], except tumor necrosis factor-α (TNF-α), had a higher level in NSCLC patients than controls. In addition, we found a moderate correlation between the TGF-β concentration and miR-20a (r = -0.537, p = 0.002) and miR-223 (r = 0.428, p = 0.015) and a weak correlation between the VEGF concentration with miR-20a (r = 0.376, p = 0.037) and miR-223 (r = -0.355, p = 0.046). MiR-145 and miR-20a are potential biomarkers for NSCLC. In addition, the regulation of tumor-promoting cytokine, through miR-20a and miR-223, might be a new therapeutic approach for lung cancer.

Dataset Information

Role of cytokines in combinatorial immunotherapeutics of non-small cell lung cancer through systems perspective.

Publications

Role of cytokines in combinatorial immunotherapeutics of non-small cell lung cancer through systems perspective.

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