Dataset Information

Circulating MicroRNAs Regulating DNA Damage Response and Responsiveness to Cisplatin in the Prognosis of Patients with Non-Small Cell Lung Cancer Treated with First-Line Platinum Chemotherapy.

ABSTRACT: The expression of microRNA (miR)-21, miR-128, miR-155, and miR-181a involved in DNA damage response (DDR) and tumor responsiveness to platinum was assessed by RT-qPCR in the plasma of patients with non-small cell lung cancer (NSCLC; n = 128) obtained prior to initiation of first-line platinum chemotherapy. U6 small nuclear RNA (snRNA) was used for normalization, and fold change of each miRNA expression relative to the expression in healthy controls was calculated by the 2-??Ct method. MicroRNA expression levels were correlated with patients' outcomes. Integrated function and pathway enrichment analysis was performed to identify putative target genes. MiR-128, miR-155, and miR-181a expressions were higher in patients compared to healthy donors. MiRNA expression was not associated with response to treatment. High miR-128 and miR-155 were correlated with shorter overall survival (OS), whereas performance status (PS) 2 and high miR-128 independently predicted for decreased OS. In the squamous (SqCC) subgroup (n = 41), besides miR-128 and miR-155, high miR-21 and miR-181a expressions were also associated with worse survival and high miR-155 independently predicted for shorter OS. No associations of miRNA expression with clinical outcomes were observed in patients with non-SqCC (n = 87). Integrated function and pathway analysis on miRNA targets revealed significant enrichments in hypoxia-related pathways. Our study shows for the first time that plasma miR-128 and miR-155 hold independent prognostic implications in NSCLC patients treated with platinum-based chemotherapy possibly related to their involvement in tumor response to hypoxia. Further studies are needed to investigate the potential functional role of these miRNAs in an effort to exploit their therapeutic potential.

SUBMITTER: Papadaki C

PROVIDER: S-EPMC7281609 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Circulating MicroRNAs Regulating DNA Damage Response and Responsiveness to Cisplatin in the Prognosis of Patients with Non-Small Cell Lung Cancer Treated with First-Line Platinum Chemotherapy.

Papadaki Chara C Monastirioti Alexia A Rounis Konstantinos K Makrakis Dimitrios D Kalbakis Konstantinos K Nikolaou Christoforos C Mavroudis Dimitrios D Agelaki Sofia S

Cancers 20200519 5

The expression of microRNA (miR)-21, miR-128, miR-155, and miR-181a involved in DNA damage response (DDR) and tumor responsiveness to platinum was assessed by RT-qPCR in the plasma of patients with non-small cell lung cancer (NSCLC; n = 128) obtained prior to initiation of first-line platinum chemotherapy. U6 small nuclear RNA (snRNA) was used for normalization, and fold change of each miRNA expression relative to the expression in healthy controls was calculated by the 2<sup>-ΔΔCt</sup> method. ...[more]

PMID: 32438598

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Project description:BackgroundDoublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown.MethodsIn this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint.ResultsOverall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167-208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405-559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142-238; hazard ratio for progression: 1.21, 95 % CI, 0.29-5.02; p = 0.27), while the median OS was 428 (95 % CI, 324-940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193-277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41-7.27; p = 0.69, while the median OS was 273 (95 % CI, 241-459) days (hazard ratio for death: 2.95; 95 % CI, 0.4-21.7; p = 0.51). Grade 3-4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients.ConclusionMoving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

Dataset Information

Circulating MicroRNAs Regulating DNA Damage Response and Responsiveness to Cisplatin in the Prognosis of Patients with Non-Small Cell Lung Cancer Treated with First-Line Platinum Chemotherapy.

Publications

Circulating MicroRNAs Regulating DNA Damage Response and Responsiveness to Cisplatin in the Prognosis of Patients with Non-Small Cell Lung Cancer Treated with First-Line Platinum Chemotherapy.

Similar Datasets

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