title: A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence.
abstract: Despite significant advances in the treatment of head and neck squamous cell carcinoma (HNSCC), the survival rate has not changed in the last decades. Therefore, the development of novel therapeutic strategies is pursued. Cancer-testis antigens (CTA) are strong immunogenic proteins with a tumor-restricted expression pattern, and are considered ideal targets for tumor-specific immunotherapeutic approaches. In this study, using an in silico approach, we selected, among 139 previously described CTA, candidates to be evaluated in 89 HNSCC and 20 normal mucosa samples. SPANX-CD (71.9%), MAGEB2 (44.9%), MAGEA1 (44.9%), MAGEB6 (32.6%), and CXORF48 (27.0%) were found frequently expressed in HNSCC, and over 85% of the tumors expressed at least one of these five CTAs. The mRNA positivity of CXORF48, MAGEB6, and CRISP2 presented significant associations with recognized clinical features for poor outcome. Furthermore, MAGEA3/6 positivity was associated with significantly better disease-free survival (DFS, P = 0.014), and the expression of this antigen was shown to be an independent prognostic factor for tumor recurrence. In conclusion, one of five selected CTAs is expressed in at least 85% of the HNSCCs, suggesting a possible usage as target for immunotherapeutic approaches, and the mRNA-positivity for MAGEA3/6 is shown to be an independent marker for DFS.
authors.affiliation: Laboratory for Cancer Molecular Biology, Department of Biological Sciences, Federal University of São Paulo, Diadema, Brazil.
authors.forename: Fernando Tadeu
authors.initials: FT
authors.lastname: Zamunér
authors.affiliation: Laboratory for Cancer Molecular Biology, Department of Biological Sciences, Federal University of São Paulo, Diadema, Brazil.
authors.forename: Bruno Takao Real
authors.initials: BT
authors.lastname: Karia
authors.affiliation: Biostatistics Department, Pio XII Foundation, Barretos Cancer Hospital, Barretos, Brazil.
authors.forename: Cleyton Zanardo
authors.initials: CZ
authors.lastname: de Oliveira
authors.affiliation: Department of Head and Neck Surgery, Pio XII Foundation, Barretos Cancer Hospital, Barretos, Brazil.
authors.forename: Carlos Roberto Dos
authors.initials: CR
authors.lastname: Santos
authors.affiliation: Department of Head and Neck Surgery, Pio XII Foundation, Barretos Cancer Hospital, Barretos, Brazil.
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Carvalho
authors.affiliation: Laboratory for Cancer Molecular Biology, Department of Biological Sciences, Federal University of São Paulo, Diadema, Brazil. Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore. andre.vettore@gmail.com.
authors.forename: André Luiz
authors.initials: AL
authors.lastname: Vettore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D013737:Testis / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C072013:MAGEA3 protein, human; C095203:MAGEA6 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger