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Using immunohistochemistry on paired non-cancerous and cancer specimens from the same patients, the study evaluates IL-10, IL10Rα and STAT3 expression across clinical stages and right- vs left-sided cancers, and tests IL-10 pathway modulation in CRC cell 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did the study measure regarding the IL-10 pathway in colon cancer progression?","Question",{"text":63,"@type":64},"The study assessed protein expression of IL-10, its receptor IL10Rα, and the intracellular signalling mediator STAT3 using immunohistochemistry.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were patients and tumours stratified for analysis?",{"text":68,"@type":64},"Data were stratified by clinical stage (early I/II vs late III/IV) and by tumour site, comparing right-sided cancers (RSCs) with left-sided cancers (LSCs).",{"name":70,"@type":61,"acceptedAnswer":71},"What functional effects did IL-10 pathway interventions produce in CRC cell lines?",{"text":72,"@type":64},"IL-10 treatment showed minimal effects, whereas IL-10Rα blockade or STAT3 inhibition induced cell cycle arrest and apoptosis in HT29 and SW620 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potential prognostic and therapeutic targets  \nAkhmed Aslam1 · Bassem Refaat1 · Riyad A. Almaimani2 · Ahmad A. Obaid3 · Abdulrahman Mujalli1 ·  \nWesam F. Farrash1 · Mohamed E. Elzubier2 · Shakir Idris1 · Afnan Salaka1 · Ahmed H. Almalki4 · MofarehY. Alkhaldi4 · Hassan A. Asiri5 · Mohammad A. Baqassi6 · Ali M. Alhanash7 · Othman M. Hakmi8 · Faisal Minshawi1  \nReceived: 21 January 2025 / Accepted: 21 April 2025  \n© The Author(s) 2025 OPEN  \nAbstract  \nBackground 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. Methods 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.  \nResults 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  \nAkhmed Aslam, Bassem Refaat and Faisal Minshawi have contributed equally to this work and share senior authorship.  \nSupplementary Information The online version contains supplementary material available at [https://doi.org/10.1007/s12672-025-](https://doi.org/10.1007/s12672-025-)[ ](https://doi.org/10.1007/s12672-025-)[02452-z](02452-z.)[.](02452-z.)  \n* Bassem Refaat, [barefaat@uqu.edu.sa](barefaat@uqu.edu.sa); [bassem.refaat@yahoo.co.uk](bassem.refaat@yahoo.co.uk); * Faisal Minshawi, [fominshawi@uqu.edu.sa |](fominshawi@uqu.edu.sa |1Department)[1](fominshawi@uqu.edu.sa |1Department)[Department](fominshawi@uqu.edu.sa |1Department)[ ](fominshawi@uqu.edu.sa |1Department)[of Clinical Laboratory Sciences](of Clinical Laboratory Sciences), [Faculty of Applied](Faculty of Applied) Medical Sciences, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, PO Box 7607, Makkah 21955, Kingdom of Saudi Arabia. 2Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, Makkah 21955, Saudi Arabia. 3Physiology Department, Faculty of Medicine, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, Makkah 21955, Saudi Arabia. 4Laboratory And Blood Bank Department, Asir Central Hospital, Prince Sultan bin Abdulaziz Road, Al-Rabwah District, Abha 62523, Saudi Arabia. 5Forensic Medicine Department, Health Affairs General Directorate in Assir, 7241 Emirate Road, Al Shifa, Abha 62521, Saudi Arabia. 6Histopathology Department, King Abdullah Medical City, Muzdalifah Road, Al Mashair, Makkah 24246, Saudi Arabia. 7Oncology Department, Asir Central Hospital, Prince Sultan bin Abdulaziz Road, Al-Rabwah District, Abha 62523, Saudi Arabia. 8Clinical Laboratory Department, Security Fo","cbCaiqiHvya3yxCd","https://ap.wps.com/l/cbCaiqiHvya3yxCd","pdf",8898807,"English","# Background\n## Colorectal cancer and tumour location\n## IL-10 signalling in cancer\n# Methods\n## Immunohistochemistry and patient stratification\n## Functional assays in CRC cell lines\n# Results\n## IL-10, IL10Rα and STAT3 expression patterns\n## Associations with clinicopathological features\n# Conclusions\n## Oncogenic potential and therapeutic targeting","[{\"question\":\"What did the study measure regarding the IL-10 pathway in colon cancer progression?\",\"answer\":\"The study assessed protein expression of IL-10, its receptor IL10Rα, and the intracellular signalling mediator STAT3 using immunohistochemistry.\"},{\"question\":\"How were patients and tumours stratified for analysis?\",\"answer\":\"Data were stratified by clinical stage (early I/II vs late III/IV) and by tumour site, comparing right-sided cancers (RSCs) with left-sided cancers (LSCs).\"},{\"question\":\"What functional effects did IL-10 pathway interventions produce in CRC cell lines?\",\"answer\":\"IL-10 treatment showed minimal effects, whereas IL-10Rα blockade or STAT3 inhibition induced cell cycle arrest and apoptosis in HT29 and SW620 cells.\"}]","Increased protein expression of interleukin-10 and its signalling molecules in colon cancer progression - potential prognostic and therapeutic targets | PDF",1790160817]