Abstract
BackgroundTafazzin (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.Methods140 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.ResultsTAZ 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.ConclusionsStrong 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.
Highlights
Tafazzin protein (TAZ) is encoded by the TAZ gene functions as a phospholipid-lysophospholipid transacylase
To identify new predictive molecules for preoperative RT and elucidate the role of TAZ protein involvement in rectal cancer patients, we investigated for the first time, the expression of TAZ protein in rectal cancer and its relationship to RT response and to clinicopathological or biological variables in the patients participating in a clinical trial of preoperative RT
Rectal cancer patients’ selection The present study included tissue sections from 140 primary rectal cancer patients, 119 distant normal mucosa specimens (109 specimens matched to the primary rectal cancer), 79 adjacent normal mucosa specimens (70 specimens matched to the primary rectal cancer), 48 lymph node metastases (44 specimens matched to the primary rectal cancer), and 101 biopsies from the primary rectal cancer patients (91 biopsies matched to the surgical primary rectal cancer) (Figure S1)
Summary
Tafazzin protein (TAZ) is encoded by the TAZ gene functions as a phospholipid-lysophospholipid transacylase. Eventhough surgery remains the curative modality for the CRC, and preoperative radiotherapy (RT) has shown a survival advantage compared to surgery alone, still the value of preoperative RT remains controversial [8,9,10]. To identify new predictive molecules for preoperative RT and elucidate the role of TAZ protein involvement in rectal cancer patients, we investigated for the first time, the expression of TAZ protein in rectal cancer and its relationship to RT response and to clinicopathological or biological variables in the patients participating in a clinical trial of preoperative RT. 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
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