Department of Pathology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
Department of Vertebrate Antibodies, Zoology Building, University of Aberdeen, Aberdeen, United Kingdom.
Int J Cancer. 2019 Aug 15;145(4):1138-1147. doi: 10.1002/ijc.32198. Epub 2019 Mar 2.
Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer related death. The aberrant expression of a brown fat-like phenotype in cancer cells has been previously implicated in tumour growth. Therefore, the expression of brown fat-associated proteins in colorectal cancer could be associated with tumour prognosis. Monoclonal antibodies to brown fat-associated proteins CIDEA, ELOVL3, ELOVL5, and UCP1 were developed. The antibodies were used to profile the expression of protein targets by immunohistochemistry in a discovery cohort comprising 50 normal colonic mucosa samples and 274 primary colorectal cancers and a validation cohort comprising 549 colorectal cancers. Immunostaining for UCP1 was observed in the majority of colorectal tumours while no immunostaining was observed in normal colonic mucosa (p < 0.001). The expression of UCP1 was significantly associated with better overall survival in both the discovery cohort (HR = 0.615, 95%CI = 0.416-0.909, χ = 6.119, p = 0.013) and the validation cohort (HR = 0.629, 95%CI = 0.480-0.825, χ = 11.558, p = 0.001). Furthermore, UCP1 was independently prognostic in multivariate analysis (p = 0.004). This study has identified the brown fat-like phenotype as a novel pathway associated with survival in colorectal cancer. The expression of UCP1 was identified as a significant prognostic biomarker for colorectal cancer.
结直肠癌是最常见的恶性肿瘤之一，也是癌症相关死亡的主要原因。先前有研究表明，癌细胞中棕色脂肪样表型的异常表达与肿瘤生长有关。因此，结直肠癌中棕色脂肪相关蛋白的表达可能与肿瘤预后相关。本文开发了针对棕色脂肪相关蛋白 CIDEA、ELOVL3、ELOVL5 和 UCP1 的单克隆抗体。这些抗体用于通过免疫组织化学在一个包含 50 个正常结肠黏膜样本和 274 个原发性结直肠癌的发现队列以及一个包含 549 个结直肠癌的验证队列中对蛋白靶标的表达进行分析。在大多数结直肠肿瘤中观察到 UCP1 的免疫染色，而在正常结肠黏膜中则没有观察到免疫染色（p<0.001）。在发现队列（HR=0.615，95%CI=0.416-0.909，χ²=6.119，p=0.013）和验证队列（HR=0.629，95%CI=0.480-0.825，χ²=11.558，p=0.001）中，UCP1 的表达与更好的总生存率显著相关。此外，UCP1 在多变量分析中是独立的预后因素（p=0.004）。本研究确定了棕色脂肪样表型是结直肠癌生存的新途径。UCP1 的表达被确定为结直肠癌的一个重要预后生物标志物。
