Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

BACKGROUND: Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. OBJECTIVE: To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. METHODS: The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. RESULTS: Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/µL or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6 ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORa⁢d⁢j, 13.265; 95% confidence intervals (CI), 2.26577.701; P= 0.006) and poor response (ORa⁢d⁢j, 15.609; 95% CI, 2.221-109.704; P= 0.006), whereas PAI-1 was an independent protective factor of poor response (ORa⁢d⁢j, 0.127; 95% CI, 0.019-0.843; P= 0.033). CONCLUSIONS: Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model.

Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer.

OBJECTIVE: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. METHODS: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. RESULTS: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019).  Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.