Prakash Shyam, Aasarey Ram, Khan Shahid, Vikram Naval K, Srivastava Saumya, Pandey Shivam, Priya Akanksha, Aggarwal Sandeep
Department of Laboratory Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Department of Laboratory Medicine, All India Institute of Medical Sciences, 2nd Floor, Room No 11, New Delhi, India.
Sci Rep. 2025 Aug 12;15(1):29470. doi: 10.1038/s41598-025-97969-2.
We investigate the role of prokineticin, T-reg cells, and oxidative metabolism in the progression of obesity-related NASH to HCC. Our findings on a cohort of 250 patients, including Obese NAFLD and Non-Obese NAFLD, reveal significant insights. In Obese NAFLD, PK-1 mRNA expression was reduced by 2.4-fold (p < 0.01) compared to Non-Obese NAFLD, while PK-2 was upregulated by 1.4-fold (p < 0.005), and FABP-5 increased by 1.4-fold (p < 0.005) compared to T2DM. IL-10 mRNA expression was 2.4-fold higher (p < 0.005) in MetS verses to Non-Obese NAFLD. Nrf-2 expression was elevated by 1.13-fold in Non-Obese NAFLD compared to Obese NAFLD (p < 0.05). Flow cytometric analysis of T-reg cells was three times lower in Obese NAFLD compared to MetS (p < 0.005), with a notable reduction in CD8 cells and an increase in CD4 cells. Correlation analysis in Obese NAFLD revealed strong positive correlations between IL-10 and T-reg (r = 1), CD4 (r = 0.99), and CD8 cells (r = 0.99). PK-1 expression correlated with CD8 cells (r = 0.52), while PK-2 negatively correlated with C-type lectin (r=-0.49). FABP-5 exhibited significant positive correlations with PK-1 (r = 0.54) and IL-10 (r = 0.63). We highlight the interplay between prokineticins, immune modulation, and metabolic oxidative factors to offer potential therapeutic targets to prevent progression to HCC, instilling hope for the future of NASH treatment.
我们研究了促动力蛋白、调节性T细胞（T-reg细胞）和氧化代谢在肥胖相关非酒精性脂肪性肝炎（NASH）进展为肝细胞癌（HCC）过程中的作用。我们对250名患者（包括肥胖型非酒精性脂肪性肝病患者和非肥胖型非酒精性脂肪性肝病患者）队列的研究结果揭示了重要见解。在肥胖型非酒精性脂肪性肝病中，与非肥胖型非酒精性脂肪性肝病相比，促动力蛋白-1（PK-1）mRNA表达降低了2.4倍（p<0.01），而促动力蛋白-2（PK-2）上调了1.4倍（p<0.005），与2型糖尿病（T2DM）相比，脂肪酸结合蛋白-5（FABP-5）增加了1.4倍（p<0.005）。与非肥胖型非酒精性脂肪性肝病相比，代谢综合征（MetS）中白细胞介素-10（IL-10）mRNA表达高2.4倍（p<0.005）。与肥胖型非酒精性脂肪性肝病相比，非肥胖型非酒精性脂肪性肝病中核因子E2相关因子2（Nrf-2）表达升高了1.13倍（p<0.05）。与代谢综合征相比，肥胖型非酒精性脂肪性肝病中T-reg细胞的流式细胞术分析结果低三倍（p<0.005），其中CD8细胞显著减少，CD4细胞增加。肥胖型非酒精性脂肪性肝病的相关性分析显示，IL-10与T-reg细胞（r=1）、CD4细胞（r=0.99）和CD8细胞（r=0.99）之间存在强正相关。PK-1表达与CD8细胞相关（r=0.52），而PK-2与C型凝集素呈负相关（r=-0.49）。FABP-5与PK-1（r=0.54）和IL-10（r=0.63）表现出显著正相关。我们强调促动力蛋白、免疫调节和代谢氧化因子之间的相互作用，以提供潜在的治疗靶点来预防进展为HCC，为NASH治疗的未来带来希望。
