Aslam Akhmed, Refaat Bassem, Almaimani Riyad A, Obaid Ahmad A, Mujalli Abdulrahman, Farrash Wesam F, Elzubier Mohamed E, Idris Shakir, Salaka Afnan, Almalki Ahmed H, Alkhaldi Mofareh Y, Asiri Hassan A, Baqassi Mohammad A, Alhanash Ali M, Hakmi Othman M, Minshawi Faisal
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, PO Box 7607, Makkah, 21955, Kingdom of Saudi Arabia.
Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, Makkah, 21955, Saudi Arabia.
Discov Oncol. 2025 Apr 29;16(1):637. doi: 10.1007/s12672-025-02452-z.
Interleukin-10 (IL-10) regulates immune responses in solid tumours, but its role in colorectal cancer (CRC) is unclear due to inconsistent findings. Tumour location is a critical prognostic factor, with proximal tumours often linked to worse outcomes. However, the relationship between IL-10 expression and tumour site is poorly understood.
Protein expression of IL-10, its α-receptor (IL10Rα), and intracellular signal transducer (STAT3) was measured by immunohistochemistry in archived paired non-cancerous and cancerous colonic specimens collected from the same patients (n = 120). The data were then stratified according to clinical stages (early-stage I/II vs. late-stage III/IV) and tumour sites (right-sided cancers; RSCs vs. left-sided cancers; LSCs). Functional effects of biologically active IL-10 protein (0.1, 1, and 40 ng/ml), anti-IL10Rα monoclonal antibody (0.1, 1, and 40 ng/ml), and a single concentration of a specific STAT3 inhibitor (2 µM) on cell cycle and apoptosis were assessed in HT29 and SW620 CRC cell lines, along with the expression of key regulatory molecules.
Overall, protein expression of IL-10, IL10Rα, and STAT3 was significantly higher in malignant tissues compared to non-malignant tissues. Early and late-stage RSCs exhibited markedly increased expression of these proteins relative to LSCs, with the highest levels observed in late-stage RSCs. Elevated protein levels of all molecules correlated with high-grade tumours, mucinous histology, lymph node metastasis, and advanced cancer stage. While IL-10 treatment showed minimal effects, IL-10Rα blockade or STAT3 inhibition led to cell cycle arrest and apoptosis in HT29 and SW620 cells, associated with increased p21, p27, and Caspase-3, and decreased CCND1, CCND3, PCNA, and survivin gene and protein expression.
IL-10 and its signalling molecules increased in CRC progression, particularly in RSCs, suggesting their potential oncogenic roles and prognostic significance. Furthermore, targeting IL-10 signalling pathways could offer a promising avenue for CRC treatment. However, further studies are required to explore the IL-10 system in relation to tumour consensus molecular subtypes to better elucidate its biological functions and prognostic values in CRC.
白细胞介素-10（IL-10）调节实体瘤中的免疫反应，但由于研究结果不一致，其在结直肠癌（CRC）中的作用尚不清楚。肿瘤位置是一个关键的预后因素，近端肿瘤通常与更差的预后相关。然而，IL-10表达与肿瘤部位之间的关系了解甚少。
通过免疫组织化学法检测从同一患者（n = 120）收集的存档配对非癌性和癌性结肠标本中IL-10及其α受体（IL10Rα）和细胞内信号转导子（STAT3）的蛋白表达。然后根据临床分期（早期I/II期与晚期III/IV期）和肿瘤部位（右侧癌症；RSCs与左侧癌症；LSCs）对数据进行分层。评估生物活性IL-10蛋白（0.1、1和40 ng/ml）、抗IL10Rα单克隆抗体（0.1、1和40 ng/ml）和单一浓度的特异性STAT3抑制剂（2 μM）对HT29和SW620 CRC细胞系的细胞周期和凋亡的功能影响，以及关键调节分子的表达。
总体而言，与非恶性组织相比，恶性组织中IL-10、IL10Rα和STAT3的蛋白表达显著更高。相对于LSCs，早期和晚期RSCs中这些蛋白的表达明显增加，在晚期RSCs中观察到最高水平。所有分子的蛋白水平升高与高级别肿瘤、黏液组织学、淋巴结转移和晚期癌症分期相关。虽然IL-10治疗显示出最小的效果，但IL-10Rα阻断或STAT3抑制导致HT29和SW620细胞的细胞周期停滞和凋亡，与p21、p27和Caspase-3增加以及CCND1、CCND3、PCNA和survivin基因及蛋白表达降低相关。
IL-10及其信号分子在CRC进展中增加，特别是在RSCs中，表明它们潜在的致癌作用和预后意义。此外，靶向IL-10信号通路可能为CRC治疗提供一个有前景的途径。然而，需要进一步研究探索IL-10系统与肿瘤共识分子亚型的关系，以更好地阐明其在CRC中的生物学功能和预后价值。
