Departments of Surgery, Trinity College Dublin, Dublin, Ireland.
Br J Surg. 2014 May;101(6):643-52. doi: 10.1002/bjs.9469. Epub 2014 Mar 24.
Oesophageal adenocarcinoma is an exemplar model of an obesity-associated adenocarcinoma. Altered secretion of adipokines by visceral fat is believed to play a key role in tumorigenesis. This study examined leptin receptor (ObR) and adiponectin receptor (AdipoR1 and AdipoR2) expression in oesophageal cancer, and its relationship with patient obesity status, clinicopathological data and patient survival.
Tissue microarrays were constructed from paraffin-embedded oesophagectomy specimens. ObR, AdipoR1 and AdipoR2 expression was quantified by immunohistochemistry. Anthropometric data were measured at the time of diagnosis, and obesity status was assessed using visceral fat area determined by computed tomography and body mass index. Receptor expression was correlated with various clinicopathological and anthropometric variables. Patient survival was estimated using the Kaplan-Meier method, and results compared between those with low versus high receptor expression. A Cox multivariable regression model was used to assess the relationship between survival and a number of co-variables.
All 125 tumours analysed expressed AdipoR1 and AdipoR2, whereas 96·8 per cent expressed ObR. There was no significant difference in tumour pathological features or patient obesity status between tumours with low versus high ObR expression. A high level of AdipoR1 expression was significantly associated with increased patient age, obesity and less advanced tumour (T) category. Expression of AdipoR2 was inversely associated with T category (P = 0.043). Low AdipoR1 expression was an independent predictor of improved overall survival (hazard ratio 0.56, 95 per cent confidence interval 0.35 to 0.90; P = 0.017).
The association between adiponectin receptor expression, obesity status and tumour category and survival suggests a potential mechanism linking obesity and oesophageal cancer.
食管腺癌是肥胖相关腺癌的典型模型。内脏脂肪分泌的脂联素改变被认为在肿瘤发生中起关键作用。本研究检测了肥胖相关腺癌中瘦素受体(ObR)和脂联素受体(AdipoR1 和 AdipoR2)的表达及其与患者肥胖状态、临床病理数据和患者生存的关系。
从石蜡包埋的食管切除术标本中构建组织微阵列。通过免疫组织化学定量检测 ObR、AdipoR1 和 AdipoR2 的表达。在诊断时测量人体测量数据,并通过计算机断层扫描确定的内脏脂肪面积和体重指数评估肥胖状态。受体表达与各种临床病理和人体测量变量相关。使用 Kaplan-Meier 方法估计患者生存,并比较低表达与高表达受体的结果。使用 Cox 多变量回归模型评估生存与多个协变量之间的关系。
分析的 125 个肿瘤均表达 AdipoR1 和 AdipoR2,而 96.8%表达 ObR。低表达 ObR 与高 ObR 表达的肿瘤之间在肿瘤病理特征或患者肥胖状态方面没有显著差异。高水平的 AdipoR1 表达与患者年龄较大、肥胖和肿瘤(T)分期较低显著相关。AdipoR2 的表达与 T 分期呈负相关(P=0.043)。低 AdipoR1 表达是总生存改善的独立预测因子(危险比 0.56,95%置信区间 0.35 至 0.90;P=0.017)。
脂联素受体表达、肥胖状态与肿瘤分期和生存之间的关系表明肥胖与食管癌之间存在潜在的机制联系。