De Nunzio Valentina, Donghia Rossella, Pesole Pasqua L, Coletta Sergio, Calò Nicola, Notarnicola Maria
National Institute of Gastroenterology-IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy.
J Clin Med. 2023 Sep 15;12(18):5986. doi: 10.3390/jcm12185986.
The tumor location in colorectal cancer (right- or left-sided colon cancer) is a key factor in determining disease progression. Right- and left-sided colon tumors are different in their clinical and molecular characteristics. Dysregulation of serum levels of proinflammatory cytokines, such as Transforming Growth Factor β (TGF-β) and Tumor Necrosis Factor-α (TNF-α), and Peroxisome Proliferator Activated Receptor-γ (PPAR-γ), known to be a growth-limiting and differentiation-promoting factor, as well as changes in miRNAs expression, are the major signaling pathways involved in the pathogenesis of this neoplasia. In the serum from 60 colorectal cancer (CRC) patients, we compared the differences in the expression of the levels of TGF-β, TNF-α, and PPAR-γ and in the expression of the main human miRNAs between right and left CRC. A significant over-expression in the TGF-β and TNF-α levels was observed in the serum from right-sided colon cancer patients. For the PPAR-γ, the patients with CRC located on the right-side showed lower levels than those detected in the serum from left-sided CRC subjects. Furthermore, significant differences also existed in the expression of specific circulating miRNAs between right- and left-sided CRC. In particular, the right upregulated miRNAs were all involved in the cell growth and proliferation related pathways. These findings confirm that the analysis of circulating levels of TGF-β, TNF-α, and PPAR-γ, as well as the study of the specific miRNAs in the serum, are able to identify specific characteristics of CRC patients, useful for choosing a personalized treatment protocol.
结直肠癌的肿瘤位置（右侧或左侧结肠癌）是决定疾病进展的关键因素。右侧和左侧结肠肿瘤在临床和分子特征方面存在差异。促炎细胞因子血清水平的失调，如转化生长因子β（TGF-β）、肿瘤坏死因子-α（TNF-α）以及过氧化物酶体增殖物激活受体-γ（PPAR-γ，已知是一种生长限制和促进分化的因子），以及微小RNA（miRNA）表达的变化，是参与这种肿瘤发病机制的主要信号通路。在60例结直肠癌（CRC）患者的血清中，我们比较了右侧和左侧CRC之间TGF-β、TNF-α和PPAR-γ水平的表达差异以及主要人类miRNA的表达差异。在右侧结肠癌患者的血清中观察到TGF-β和TNF-α水平显著过度表达。对于PPAR-γ，右侧CRC患者的水平低于左侧CRC受试者血清中检测到的水平。此外，右侧和左侧CRC之间特定循环miRNA的表达也存在显著差异。特别是，右侧上调的miRNA均参与细胞生长和增殖相关途径。这些发现证实，分析TGF-β、TNF-α和PPAR-γ的循环水平以及研究血清中的特定miRNA，能够识别CRC患者的特定特征，有助于选择个性化的治疗方案。
