Evaluation of Circulating MicroRNAs as Biomarkers of Hematological Adverse Reactions in Lung Cancer Patients Treated with Carboplatin and Paclitaxel

• Published in: Drug safety Vol. 45; no. 10; pp. 1168 - 1169
• Main Authors: Moriel, P, Vasconcelos, P E N S, Seguin, C S, Geraldo, M V, Barbeiro, A D S, Zambon, L, Pincinato, E D C, Junior, M W P
• Format: Journal Article
• Language: English
• Published: Auckland Springer Nature B.V 01.10.2022
• Subjects: Adenocarcinoma; Anemia; Bioinformatics; Biomarkers; Carboplatin; Chemotherapy; Genes; Hematology; Hematopoiesis; Hematopoietic system; Lung cancer; MicroRNAs; miRNA; Morbidity; Paclitaxel; Patients; Quality of life; Runx1 protein; Side effects; Smoking; Toxicity; Tumors
• ISSN: 0114-5916; 1179-1942

Introduction: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide [1]. The treatment of lung cancer initially depend on the definition of the type of tumor and its staging [2]. The most common treatment is chemotherapy and the first line of treatment is the combination of carboplatin and paclitaxel. The effectiveness of this treatment is low and presents a high prevalence of adverse reactions, especially hematological [3]. Studies of new biomarkers, such as circulating miRNAs, related to these adverse reactions are very important to optimize the quality of life of patients. Objective: To verify a relation between circulating miRNAs and hematologic adverse reactions caused by treatment with carboplatin and paclitaxel in lung cancer patients. Methods: This study was approved by the ethics committee no. 83196318.8.0000.5404. Blood was collected from patients before and 15 days after chemotherapy, for hematological adverse reactions analysis, for MicroArray and for qPCR validation. Adverse reactions were classified according to the Common Terminology Criteria for Adverse Events v4.0 [4]. The MicroArray was performed with plasma from 6 patients without and 6 patients with hematological adverse reactions. Three miRNAs identified by MicroArray were validated via qPCR using 20 patients without and 26 with hematological adverse reactions. Bioinformatics analyses were performed by miRwalk, DAVID and GeneMani. Results: Patients with lung cancer treated with carboplatin and paclitaxel are mostly white, with a mean age of 63.50 years, retired, with low schooling, heavy smokers, not eligible for surgical resection, with histopathological diagnosis of adenocarcinoma and stage 4. We observed a high prevalence of grades above 0 for anemia (44%). The MicroArray of patients with and without hematological toxicity verified 9 differently expressed plasma miRNAs among these patients. Of these 3 were chosen for validation being miR-1273g-3p, miR- 3613-5p and miR-455-3p. Only miR-455-3p showed a significant expression reduction (p = 0.04) between the groups, before chemotherapy with carboplatin and paclitaxel. The bioinformatics analysis of hsa-miR-455-3p showed an important relationship of this miRNA with the hematopoiesis pathway, especially with action on the RUNX1 and TAL1 genes. Conclusion: The most prevalent adverse reactions in lung cancer patients treated with carboplatin and paclitaxel were hematological, especially anemia. This adverse reaction, caused by a dysfunction of the hematopoietic system, can be explained by a possible relation between important genes in this system, RUNX1 and TAL1, and hsamiR- 455-3p.