RESUMO
BACKGROUND: No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. METHODS: We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. RESULTS: MiR-3168 (p = 1.98 × 10- 8), miR-4718 (p = 4.24 × 10- 5), and miR-6125 (p = 6.60 × 10- 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00-1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03-2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98-3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61-0.93) with sensitivity of 66.76 and specificity of 79.49. CONCLUSIONS: We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.
Assuntos
Injúria Renal Aguda/epidemiologia , Biomarcadores Tumorais/metabolismo , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Creatinina/sangue , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Curva ROC , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Análise de Sequência de RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Antiphospholipid antibodies induce a pro-inflammatory and hypercoagulable state that lead to increased risk of thrombosis. Whether oxidative damage contributes thrombosis risk is a matter of debate. We evaluated the association between oxidative stress and thrombosis in primary antiphospholipid syndrome (t-PAPS). Plasma total antioxidant capacity and the levels of malondialdehyde (TBARs), carbonyl protein, and 8-isoprostane in plasma were determined in a group of patients with t-PAPS and in individuals without a history of thrombosis (controls) using commercial ELISA assays. The levels of these plasma markers of oxidative stress were compared between t-PAPS and controls using Mann-Whitney test. A total of 70 patients with t-PAPS and 74 controls were included. Overall, measurements of all plasma oxidative stress markers were similar between t-PAPS patients and controls. In a subgroup analysis, patients with t-PAPS and arterial thrombosis had a higher antioxidant capacity as compared to controls. Thrombotic PAPS was not associated with increased levels of oxidative stress markers, in comparison with individuals without thrombosis. Even though it is not possible to rule out that a mild oxidative damage, not detected by plasma markers, occurs in t-PAPS, our results suggest that measuring plasma oxidative stress markers has limited clinical relevance in t-PAPS.
Assuntos
Síndrome Antifosfolipídica , Trombose , Anticorpos Antifosfolipídeos , Antioxidantes , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Biomarcadores/sangue , Humanos , Estresse Oxidativo , Trombose/sangue , Trombose/etiologiaRESUMO
Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20 days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX™Red, H2DCF-DA, and Amplex® Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5 days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O 2â¢- ), hydrogen peroxide (H2O2), and general reactive oxygen species production occurred. A higher production of H2O2 was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between H2O2 production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5 days following cisplatin administration. In conclusion, H2O2 production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.
Assuntos
Cisplatino , Neoplasias de Cabeça e Pescoço , Peróxido de Hidrogênio/sangue , Nefropatias , Leucócitos Mononucleares , Estresse Oxidativo/efeitos dos fármacos , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/patologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. METHODS: We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. RESULTS: MiR-3168 (p = 1.98 × 10− 8 ), miR-4718 (p = 4.24 × 10− 5 ), and miR-6125 (p = 6.60 × 10− 5 ) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.001.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03 2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.983.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.610.93) with sensitivity of 66.76 and specificity of 79.49. CONCLUSIONS: We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.