Tafazzin protein expression is associated with tumorigenesis and radiation response in rectal cancer: a study of Swedish clinical trial on preoperative radiotherapy

• Published in: PloS one Vol. 9; no. 5; p. e98317
• Main Authors: Pathak, Surajit, Meng, Wen-Jian, Zhang, Hong, Gnosa, Sebastian, Nandy, Suman Kumar, Adell, Gunnar, Holmlund, Birgitta, Sun, Xiao-Feng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.05.2014; Public Library of Science (PLoS)
• Subjects: Adaptor Proteins, Signal Transducing - biosynthesis; Adult; Aged; Apoptosis; Bioindicators; Biomarkers; Biomarkers, Tumor - biosynthesis; Biopsy; Brain cancer; Cancer; Cancer research; Cancer therapies; Cancer treatment; Carcinogenesis; Carcinogens; Cardiolipin; Cell adhesion & migration; Chemotherapy; Clinical trials; Colorectal cancer; Councils; Female; Gene expression; Gene Expression Regulation, Neoplastic; Health risk assessment; Health sciences; Humans; Immunohistochemistry; Inflammation; Inhibitor of Apoptosis Proteins - biosynthesis; Lymph; Lymph nodes; Lymphatic Metastasis; Male; Medicin; Medicine; Medicine and Health Sciences; Membrane lipids; Membrane Proteins - biosynthesis; Metastases; Middle Aged; Mitochondria; Mucosa; Mutation; Neoplasm Proteins - biosynthesis; Neoplasm Staging; Oncology; Patients; Protein interaction; Protein-protein interactions; Proteins; Radiation; Radiation (Physics); Radiation therapy; Radiotherapy; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Rectum; Signal transduction; Structure-function relationships; Surgery; Transcription Factors - biosynthesis; Tumorigenesis; Tumors; Sweden; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098317

Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT. 140 rectal cancer patients were included in this study, of which 65 received RT before surgery and the rest underwent surgery alone. TAZ expression was determined by immunohistochemistry in primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In-silico protein-protein interaction analysis was performed to study the predictive functional interaction of TAZ with other oncoproteins. TAZ showed stronger expression in primary cancer and lymph node metastasis compared to distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ expression was significantly higher in stages I-III and non-mucinious cancer of non-RT patients. In RT patients, strong TAZ expression in biopsy was related to distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR, 6.160, 95% CI, 1.063-35.704). In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and FXYD-3. Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.