The Effect and Mechanism of Subcutaneous and Visceral Adipose Tissue Loss on Gastric Cancer Patients With Cachexia

Background: Adipose tissue loss is one of the features in patients with cancer cachexia. However, whether subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) contribute differently to the progress of cancer cachexia in gastric cancer patients with cachexia remains unclear. We aim to investigate the effect of SAT and VAT in gastric cancer patients with cachexia and the underlying molecular mechanism. Methods: Gastric cancer patients who underwent surgery were divided into cancer cachexia group and non-cachexia group. A new deep learning system was developed to segment SAT and VAT from the computed tomography images at the third lumbar vertebra. Indexes of SAT (SATI) and VAT (VATI) were compared between cachexia and non-cachexia groups. The prognostic values of SATI and VATI for patients with gastric cancer cachexia were analyzed by Kaplan-Meier method and Cox regression. Whole transcriptome RNA sequencing was performed to compare the different gene expressions between SAT and VAT in gastric cancer patients with cachexia. Results: A total of 1627 gastric cancer patients (411 cachexia and 1216 non-cachexia) were included in this study. A new V-Net-Based segmentation deep learning system was developed to quickly (0.02 seconds/image) and accurately segment SAT (dice scores = 0.96) and VAT (dice scores = 0.98). The SATI of gastric cancer patients with cachexia were significantly lower than non-cachexia patients (44.91 ± 0.90 vs. 50.92 ± 0.71 cm2/m2, P < 0.001), whereas no significant difference was detected in VATI (35.98 ± 0.84 VS. 37.90 ± 0.45 cm2/m2, P= 0.076). Cachexia patients with low SATI showed poor survival than those with high SATI (HR = 1.35; 95% CI = 1.06-1.74). In contrast, VATI did not show close correlation with survival in patients with cachexia (HR = 1.18; 95% CI = 0.92-1.51). We detected 113 upregulated genes and 342 downregulated genes when comparing SAT to VAT in gastric cancer patients with cachexia. GO and KEGG analyses indicated that immune response might contribute to the difference between SAT and VAT. Conclusion: SAT and VAT showed different effects on gastric cancer patients with cachexia. Various genes might play important roles in the different loss of SAT and VAT in cancer cachexia. More attention should be given to the loss of SAT during the progress. Funding Statement: This work was supported by grants from the Youth of National Natural Science Foundation of China (81803091). Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: Ethics committee of Zhongshan Hospital of Fudan University approved this study (B2013-106R).