title: Clinical evaluation of M30 and M65 ELISA cell death assays as circulating biomarkers in a drug-sensitive tumor, testicular cancer.
abstract: Circulating full-length and caspase-cleaved cytokeratin 18 (CK18) are considered biomarkers of chemotherapy-induced cell death measured using a combination of the M30 and M65 ELISAs. M30 measures caspase-cleaved CK18 produced during apoptosis and M65 measures the levels of both caspase-cleaved and intact CK18, the latter of which is released from cells undergoing necrosis. Previous studies have highlighted their potential as prognostic, predictive, and pharmacological tools in the treatment of cancer. Disseminated testicular germ cell cancer (TC) is a paradigm for a chemosensitive solid malignancy of epithelial origin and has a cure rate of 80% to 90%. We conducted M30/M65 analyses on 34 patients with TC before and during treatment with bleomycin, etoposide, and cisplatin and showed that prechemotherapy serum levels of M65 and M30 antigens are correlated with established TC tumor markers lactate dehydrogenase, alpha-fetoprotein, and beta-human chorionic gonadotropin, probably reflecting tumor load. Cumulative percentage change of M65 and M30 from baseline to end of study was highest in poor prognosis patients (P < .05). Moreover, area under the curve profiles of M65 and M30 during chemotherapy mirrored dynamic profiles for lactate dehydrogenase, alpha-fetoprotein, and beta-human chorionic gonadotropin. Consequently, M65 and M30 levels appear to reflect chemotherapy-induced changes that correlate with changes in markers routinely used in the clinic for management of patients with TC. This is the first clinical study where M65 and M30 antigen levels correlate with established prognostic markers and provides impetus for their exploration in other epithelial cancers where there is a pressing need for informative circulating biomarkers.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Haas
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Pietro
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Simpson
authors.forename: Coby
authors.initials: C
authors.lastname: Meijer
authors.forename: Albert J H
authors.initials: AJ
authors.lastname: Suurmeijer
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Lancashire
authors.forename: J
authors.initials: J
authors.lastname: Cummings
authors.forename: Steven
authors.initials: S
authors.lastname: de Jong
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Caroline
authors.initials: C
authors.lastname: Dive
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis / Q000097:blood / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D053538:Keratin-18 / Q000032:analysis* / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D011379:Prognosis; D013736:Testicular Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053538:Keratin-18; D020169:Caspases