SERPINB1 expression is predictive for sensitivity and outcome of cisplatin-based chemotherapy in melanoma

Abstract

Despite of highly effective new therapeutic strategies, chemotherapy still is an important treatment option in metastatic melanoma. Since predictors of chemotherapy response are rare, drugs and regimens are currently chosen arbitrarily. The present study was aimed at the identification of molecular markers predicting the outcome of chemotherapy in melanoma. Tumor biopsies from metastatic lesions were collected from 203 stage IV melanoma patients prior to chemotherapy onset and used for gene expression profiling (n = 6; marker identification set), quantitative real-time PCR (n = 127; validation set 1), and immunohistochemistry on tissue microarrays (n = 70; validation set 2). The results were correlated to the tumors' in-vitro chemosensitivity and to the patients' in-vivo chemotherapy outcome. SERPINB1 was found to correlate to the in-vitro sensitivity to cisplatin-containing chemotherapy regimens (p = 0.005). High SERPINB1 gene expression was associated with favorable tumor response (p = 0.012) and prolonged survival (p = 0.081) under cisplatin-based chemotherapy. High SERPINB1 protein expression in tumor tissue from cisplatin-treated patients was associated with a favorable survival (p = 0.011), and proved as an independent predictor of survival (p = 0.008) by multivariate analysis. We conclude, that SERPINB1 expression, although not functionally involved, is predictive for the outcome of cisplatin-based chemotherapy in melanoma, and thus may be useful to personalize melanoma chemotherapy.

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

“…SERPINB1 levels were found decreased in patients with prostate cancer, glioma, and HCC, favoring migration and invasion [75][76][77], while displaying increased expression in cells and patients with oral cancer, correlating with high motility and cell migration in vitro [78]. Importantly, SERPINB1 levels were shown to predict the outcome of cisplatin-based chemotherapies in melanoma [79] and the value of this transcript/protein as surrogate marker for CCA should be evaluated in the future.…”

Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma

“…High expression of SerpinB1 has been linked to increased sensitivity towards cisplatin-based chemotherapy and increased survival in melanoma. 53 Since cisplatin is a standard chemotherapeutic agent in treatment protocol of pediatric medulloblastoma, the improved survival might be related to increased cisplatin sensitivity, rather than to a SerpinB1 dependent immunomodulatory effect.…”

Infiltrating Myeloid Cells Exert Protumorigenic Actions via Neutrophil Elastase

“…Intriguingly, endogenous NE inhibitors, like SERPINB1 and elafin, are ubiquitously expressed, and their down-regulation in cancer cells is associated with aggressive phenotypes (12, 44, 45). In addition to protease inhibitory functions, these proteins are important in anti-microbial, anti-inflammatory, and apoptotic pathways, and in fact can diminish NET formation (46, 47).…”