Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma.
BACKGROUND
Obesity is associated with oesophageal adenocarcinoma, but mechanisms linking fat and carcinogenesis remain poorly understood. Altered circulating adipocytokines may be important. This study aimed to identify pathways through which visceral fat impacts on tumour biology.


METHODS
Seventy-five patients with oesophageal adenocarcinoma underwent anthropometric and radiological assessment of obesity. Expression of leptin receptor (ObR) and adiponectin receptors 1 and 2 (AdipR1, AdipR2) was quantified by real-time reverse transcriptase-polymerase chain reaction. The human oesophageal adenocarcinoma cell line OE33 was used as the calibrator sample.


RESULTS
Ninety-one per cent of tumours expressed ObR, 95 per cent expressed AdipR1 and 100 per cent expressed AdipR2. Relative expression of ObR was upregulated in 67 per cent, and AdipR1 and AdipR2 were downregulated in 55 and 68 per cent respectively, relative to the calibrator sample. Upregulated ObR and AdipR2 expression was significantly associated with anthropometric and radiological measures of obesity. Upregulated ObR was associated with advanced tumour and node category (P = 0.036 and P = 0.025 respectively), and upregulated AdipR2 with nodal involvement (P = 0.037).


CONCLUSIONS
Obesity is associated with upregulated ObR and AdipR2 expression in oesophageal adenocarcinoma. The association of ObR and AdipR2 with tumour stage suggest that pathways involving adipocytokines affect tumour biology.
Howard
J M
JM
Department of Surgery, Trinity College Dublin and St James's Hospital, Dublin, Ireland.
Beddy
P
P
Ennis
D
D
Keogan
M
M
Pidgeon
G P
GP
Reynolds
J V
JV
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D054392:Adipokines / Q000378:metabolism; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D056128:Obesity, Abdominal / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D054419:Receptors, Adiponectin / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism*; D015854:Up-Regulation
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D054392:Adipokines; D054419:Receptors, Adiponectin; D054411:Receptors, Leptin