Meng Qingcai, Fang Zengli, Mao Xiaoqi, Tang Rong, Liang Chen, Hua Jie, Wang Wei, Shi Si, Yu Xianjun, Xu Jin
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Comput Struct Biotechnol J. 2023 Apr 7;21:2631-2639. doi: 10.1016/j.csbj.2023.04.003. eCollection 2023.
Intratumor heterogeneity of positron emission tomography-computed tomography (PET-CT) is reflected by variable F-fluorodeoxyglucose (FDG) uptake. Increasing evidence has shown that neoplastic and non-neoplastic components can affect the total F-FDG uptake in tumors. Cancer-associated fibroblasts (CAFs) is considered as the main non-neoplastic components in tumor microenvironment (TME) of pancreatic cancer. Our study aims to explore the impact of metabolic changes in CAFs on heterogeneity of PET-CT. A total of 126 patients with pancreatic cancer underwent PET-CT and endoscopic ultrasound elastography (EUS-EG) before treatment. High maximum standardized uptake value (SUVmax) from the PET-CT was positively correlated with the EUS-derived strain ratio (SR) and indicated poor prognosis of patients. In addition, single-cell RNA analysis showed that CAV1 affected glycolytic activity and correlated with glycolytic enzyme expression in fibroblasts in pancreatic cancer. We also observed the negative correlation between CAV1 and glycolytic enzyme expression in the tumor stroma by using immunohistochemistry (IHC) assay in the SUVmax-high and SUVmax-low groups of pancreatic cancer patients. Additionally, CAFs with high glycolytic activity contributed to pancreatic cancer cell migration, and blocking CAF glycolysis reversed this process, suggesting that glycolytic CAFs promote malignant biological behavior in pancreatic cancer. In summary, our research demonstrated that the metabolic reprogramming of CAFs affects total F-FDG uptake in tumors. Thus, an increase in glycolytic CAFs with decreased CAV1 expression promotes tumor progression, and high SUVmax may be a marker for therapy targeting the neoplastic stroma. Further studies should clarify the underlying mechanisms.
正电子发射断层扫描-计算机断层扫描（PET-CT）的肿瘤内异质性通过氟代脱氧葡萄糖（FDG）摄取的变化得以体现。越来越多的证据表明，肿瘤性和非肿瘤性成分均可影响肿瘤中总的F-FDG摄取。癌症相关成纤维细胞（CAFs）被认为是胰腺癌肿瘤微环境（TME）中的主要非肿瘤性成分。我们的研究旨在探讨CAFs代谢变化对PET-CT异质性的影响。共有126例胰腺癌患者在治疗前接受了PET-CT和内镜超声弹性成像（EUS-EG）检查。PET-CT测得的高最大标准化摄取值（SUVmax）与EUS衍生的应变率（SR）呈正相关，提示患者预后不良。此外，单细胞RNA分析显示，CAV1影响糖酵解活性，并与胰腺癌成纤维细胞中的糖酵解酶表达相关。我们还通过免疫组织化学（IHC）检测，观察了胰腺癌患者SUVmax高组和SUVmax低组肿瘤基质中CAV1与糖酵解酶表达之间的负相关关系。此外，具有高糖酵解活性的CAFs促进胰腺癌细胞迁移，而阻断CAF糖酵解可逆转这一过程，这表明糖酵解的CAFs促进了胰腺癌的恶性生物学行为。总之，我们的研究表明，CAFs的代谢重编程影响肿瘤中总的F-FDG摄取。因此，CAV1表达降低的糖酵解CAFs增加会促进肿瘤进展，高SUVmax可能是靶向肿瘤基质治疗的一个标志物。进一步的研究应阐明其潜在机制。
