Cohesin subunits, STAG1 and STAG2, and cohesin regulatory factor, PDS5b, in oral squamous cells carcinomas

• Published in: Journal of oral pathology & medicine 2017-03, Vol.46 (3), p.188-193
• Main Authors: França, Josiane Alves, Diniz, Marina Gonçalves, Bernardes, Vanessa Fátima, Costa‐Silva, Raíssa Cristina, Souza, Renan Pedra, Gomez, Ricardo Santiago, Gomes, Carolina Cavaliéri
• Format: Article
• Language: English
• Subjects: Antigens, Nuclear - genetics; Antigens, Nuclear - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell cycle; cell cycle genes; Cell proliferation; Cohesin; Dentistry; DNA-Binding Proteins - metabolism; Heterozygosity; Humans; Immunohistochemistry; Ki-67 Antigen - metabolism; Loss of Heterozygosity; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mucosa; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; p53 Protein; PDS5B; Regression analysis; Reverse Transcriptase Polymerase Chain Reaction; Squamous cell carcinoma; STAG1; STAG2; Transcription; Transcription Factors - metabolism; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.12474

Background Cohesin complex is responsible for sister chromatid cohesion. STAG1/STAG2 is part of the complex, which is regulated by PDS5B. Alterations in these genes were described in tumors. PDS5B is a negative regulator of cell proliferation. We aimed to assess molecular alterations in these genes in oral squamous cell carcinoma (OSCC) and predict their expression by the expression of 84 cell cycle genes. In addition, we investigated whether pds5b protein expression impacted ki‐67 and p53 immunopositivity. Methods We assessed loss of heterozygosity (LOH) at STAG1 and STAG2 loci in 15 OSCC using three polymorphic markers. Associations between the immunoexpression of pds5b and ki‐67 and p53 were tested in 62 samples. Differences between transcriptional levels of STAG1, STAG2, and PDS5B between OSCC and normal oral mucosa (NM) were evaluated by qPCR. An 84 cell cycle genes qPCR array was carried with OSCC samples, and STAG1, STAG2, and PDS5B were independently used as response variables in multiple linear regression models. Results Loss of heterozygosity in at least one marker was observed in three samples. pds5b, p53, and ki‐67 were highly expressed, and no association was found between pds5b immunoexpression and ki‐67 or p53 (P > 0.05). OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. STAG1 and CUL3 expression seem to be related (P = 0.004). Conclusions There is LOH at STAG1 and STAG2 loci in OSCC, but OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. pds5b immunoexpression in OSCC was high, but it was not associated with proliferation cell index.