title: Resistance to platinum-containing chemotherapy in testicular germ cell tumors is associated with downregulation of the protein kinase SRPK1.
abstract: Male germ cell tumors (GCTs) are extremely sensitive to platinum-containing chemotherapy, with only 10% of patients showing therapy resistance. However, the biological basis of the high curability of disseminated GCTs by chemotherapy is still unknown. Recently, we demonstrated that the mammalian serine/arginine-rich protein-specific kinase 1 (SRPK1) is a cisplatin-sensitive gene, inactivation of which leads to cisplatin resistance. Because, in mammalians, the expression of SRPK1 is preferentially high in testicular tissues, cisplatin responsiveness of male GCTs might be associated with SRPK1 levels. In the present study, we monitored SRPK1 protein expression in a unique series of nonseminomatous GCTs by immunohistochemistry. Randomly selected GCTs (n = 70) and tumors from patients responding to standard chemotherapy (n = 20) generally showed strong SRPK1 staining. In contrast, expression in refractory GCTs (n = 20) as well as in GCTs from poor-prognosis patients responding to high-dose chemotherapy only (n = 11) was significantly lower (two-sided Wilcoxon rank sum test: P < .001). In conclusion, our data suggest that SRPK1 expression might be an important prognostic indicator for the chemoresponsiveness of nonseminomatous GCTs.
authors.affiliation: Department of Medical Oncology, Erasmus-MC, Rotterdam, The Netherlands.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Schenk
authors.forename: Hans
authors.initials: H
authors.lastname: Stoop
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Frank
authors.initials: F
authors.lastname: Mayer
authors.forename: Gerrit
authors.initials: G
authors.lastname: Stoter
authors.forename: J Wolter
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: Erik
authors.initials: E
authors.lastname: Wiemer
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
authors.forename: Kees
authors.initials: K
authors.lastname: Nooter
mesh_terms: D000293:Adolescent; D000328:Adult; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
chemical_list: D017671:Platinum Compounds; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases