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对伴有和不伴有恶病质的新诊断胃肠道癌患者皮下脂肪组织中褐变标志物的评估。

Evaluation of Browning Markers in Subcutaneous Adipose Tissue of Newly Diagnosed Gastrointestinal Cancer Patients with and without Cachexia.

作者信息

Molfino Alessio, Belli Roberta, Imbimbo Giovanni, Carletti Raffaella, Amabile Maria Ida, Tambaro Federica, di Gioia Cira R T, Belloni Elena, Ferraro Elisabetta, Nigri Giuseppe, Muscaritoli Maurizio

机构信息

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy.

出版信息

Cancers (Basel). 2022 Apr 12;14(8):1948. doi: 10.3390/cancers14081948.

Abstract

We assessed the molecular phenotype of the browning of white adipose tissue in newly diagnosed cancer patients and controls undergoing surgery for gastrointestinal tumors and for non-malignant diseases, respectively. We collected subcutaneous adipose tissue (SAT) samples and using RT-PCR, we analyzed the expression of markers of browning and using Western blot the protein levels of UCP1 and PGC1α. The mRNA levels were lower in cancer patients vs. controls ( = 0.01), whereas and mRNA levels were higher in cancer patients. We found higher PGC1α protein levels in patients vs. controls, while no differences were seen for UCP1. The expression was lower in cachectic and non-cachectic patients vs. controls, whereas expression was higher in cachectic and non-cachectic patients vs. controls. mRNA levels were higher in cachectic vs. non-cachectic patients ( = 0.03) vs. controls ( = 0.016). According to type of tumors, we did not observe differences in expression, whereas was higher in pancreatic cancer vs. colorectal and vs. controls. We observed the lower expression of in pancreatic and colorectal cancer vs. controls. We documented higher UCP1 protein levels in pancreatic cancer patients vs. colorectal ( = 0.002) and vs. controls ( = 0.031). PGC1α protein levels were higher in pancreatic cancer patients vs. controls. Different markers of the browning of SAT are modulated, and pancreatic cancer showed changes in UCP1 and PGC1α; PGC1α was highly expressed in cachectic patients, with clinical implications that should be further clarified.

摘要

我们分别评估了新诊断癌症患者以及接受胃肠道肿瘤手术和非恶性疾病手术的对照组白色脂肪组织褐变的分子表型。我们收集了皮下脂肪组织(SAT)样本,通过逆转录聚合酶链反应(RT-PCR)分析褐变标志物的表达,并利用蛋白质免疫印迹法检测解偶联蛋白1(UCP1)和过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1α)的蛋白质水平。癌症患者的信使核糖核酸(mRNA)水平低于对照组(P = 0.01),而某些mRNA水平在癌症患者中较高。我们发现患者的PGC1α蛋白质水平高于对照组,而UCP1未见差异。在恶病质和非恶病质患者中,某基因的表达低于对照组,而另一基因的表达在恶病质和非恶病质患者中高于对照组。恶病质患者的mRNA水平高于非恶病质患者(P = 0.03)以及对照组(P = 0.016)。根据肿瘤类型,我们未观察到某基因表达的差异,而胰腺癌中另一基因的表达高于结直肠癌及对照组。我们观察到胰腺癌和结直肠癌中某基因的表达低于对照组。我们记录到胰腺癌患者的UCP1蛋白质水平高于结直肠癌患者(P = 0.002)以及对照组(P = 0.031)。胰腺癌患者的PGC1α蛋白质水平高于对照组。SAT褐变的不同标志物受到调节,胰腺癌显示出UCP1和PGC1α的变化;PGC1α在恶病质患者中高表达,其临床意义有待进一步阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c773/9025935/2e4cd93b3aab/cancers-14-01948-g001.jpg

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