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Integrated bioinformatics identified leptin (LEP) as a candidate gene linked to colorectal cancer liver metastasis (CRLM). Overexpression of LEP promoted CRC cell proliferation, invasion, and metastatic potential in vitro, while LEP suppression showed the opposite effects. Lipid staining and a CRLM murine model suggested that LEP enhances hepatic metastasis and induces tumor-associated macrophage M2 polarization, supported by immunofluorescence, qRT-PCR, and ELISA. Results indicate LEP may modulate CRLM via lipid rewiring and immunosuppressive macrophage polarization, motivating further biomarker and therapeutic target evaluation.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/potential-role-of-leptin-in-colorectal-cancer-liver-metastasis-involving-lipid-metabolic-reprogramming-and-immunosuppressive-macrophage-polarization/356955/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/potential-role-of-leptin-in-colorectal-cancer-liver-metastasis-involving-lipid-metabolic-reprogramming-and-immunosuppressive-macrophage-polarization/356955.png","ImageObject",300,407,{"name":92,"@type":93},"eBook King","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23",true,{"@type":101,"interactionType":102,"userInteractionCount":14},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"Why is colorectal cancer liver metastasis clinically difficult to treat?","Question",{"text":111,"@type":112},"Only 10–20% of patients with hepatic metastases qualify for curative resection. Many are diagnosed in middle-to-late stages and multiple or extrahepatic metastases make surgery challenging, leaving long-term outcomes suboptimal despite systemic therapies.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What evidence links leptin (LEP) to colorectal cancer liver metastasis?",{"text":116,"@type":112},"Integrated bioinformatics linked LEP to CRLM, and functional assays showed LEP overexpression enhanced CRC cell proliferation, invasion, and metastatic potential. In vivo, a CRLM murine model supported LEP involvement in hepatic metastasis and M2 macrophage polarization.",{"name":118,"@type":109,"acceptedAnswer":119},"How does LEP relate to lipid metabolism and immune macrophages in the proposed mechanism?",{"text":120,"@type":112},"Lipid staining indicated LEP-associated lipid metabolic alterations. Immunofluorescence, qRT-PCR, and ELISA further supported that LEP correlates with increased M2 macrophage markers and related cytokines, suggesting immunosuppressive polarization contributes to CRLM progression.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},356955,1790193100,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962088006270,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nPotential role of leptin in colorectal cancer liver metastasis involving lipid metabolic reprogramming and immunosuppressive macrophage polarization  \nYuchen Xie1,2,3,7, Hongyu Wang1,2,3,7, Xiao Dong4,7, Yueran Chen5, Yidong Xia1,2,3,  \nXueying Huang4, Wenling Zhang6􀀍, Shipeng Dai1,2,3􀀍, Yichan Zhou4􀀍 & Xiaofeng Qian1,2,3􀀍  \nLiver metastasis, a hallmark of advanced Colorectal cancer (CRC), represents the leading cause of mortality in affected patients. While surgical resection of primary tumors and metastatic lesions remains the gold-standard therapeutic intervention, only 10–20% of patients with hepatic metastases qualify for curative resection, underscoring the critical need for novel therapeutic strategies. Through integrated bioinformatics analysis, we identified Leptin (LEP) as a potential candidate gene associated with colorectal cancer liver metastasis (CRLM). Functional analyses including colony formation, wound healing and cross-well migration indicated that LEP overexpression was associated with enhanced proliferation, invasion and metastasis potential ofCRC cells, and vice versa. Mechanistically, Nile Red lipid staining revealed potential lipid metabolic alterations linked to LEP levels in CRC cells. In vivo, a CRLM murine model suggested the potential involvement of LEP in promoting hepatic metastasis and inducing tumor-associated macrophage M2 polarization. Immunofluorescence (IF), quantitative realtime PCR (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA) analyses further supported the correlation between LEP and the upregulation of M2-macrophage markers and associated cytokines. These findings suggest that LEP may function as a candidate modulator of CRLM progression through lipid metabolism rewiring and immunosuppressive macrophage polarization, warranting further investigation into its potential as a diagnostic biomarker or therapeutic target for metastatic CRC.  \nKeywords Colorectal cancer liver metastasis, Leptin, Lipid metabolism, Macrophage polarization  \nColorectal cancer (CRC) is one of the most prevalent malignant tumors globally, constituting 10% of all cancer cases and ranking as the third most common cancer worldwide1,2. CRC predominantly affects individuals over the age of 50, though the proportion of younger patients has been on the rise in recent years3. Lifestyle factors including high-fat diets, insufficient dietary fiber intake, obesity, lack of physical activity, smoking, and excessive alcohol consumption are recognized as primary risk factors for CRC3. Genetic predispositions, such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, also elevate the risk of CRC3. Patients with long-term chronic inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease, are additionally at heightened risk for CRC4.  \nColorectal cancer liver metastasis (CRLM) is a frequent complication in advanced cases and a significant cause of mortality among colorectal cancer patients5. Liver resection is an effective therapeutic option for patients with solitary or a few localized liver metastases, provided the primary tumor has been or can be resected6,7. However, due to the absence of specific early screening methods, numerous patients are diagnosed in  \n1Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China. 3NHC Key Laboratory of Hepatobiliary Cancers, Nanjing, China. 4Department of Geriatric Gastroenterology, The First Afffliated Hospital of Nanjing Medical University, Nanjing, China. 5Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. 6Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 7Yuchen Xie, Hongyu Wang and Xiao Dong contributed equall","cbCaij8S0N33F7yL","https://ap.wps.com/l/cbCaij8S0N33F7yL","pdf",3281034,17,"English","# Introduction\n# Methods and Data Resources\n## Bioinformatics analysis (TCGA COAD dataset)\n# Results\n## LEP expression and prognosis association\n## LEP function in CRC cell behaviors\n## Lipid metabolic alterations linked to LEP\n## In vivo CRLM model and macrophage polarization\n## Molecular validation (IF, qRT-PCR, ELISA)\n# Discussion and Implications\n## Diagnostic biomarker and therapeutic target potential","[{\"question\":\"Why is colorectal cancer liver metastasis clinically difficult to treat?\",\"answer\":\"Only 10–20% of patients with hepatic metastases qualify for curative resection. Many are diagnosed in middle-to-late stages and multiple or extrahepatic metastases make surgery challenging, leaving long-term outcomes suboptimal despite systemic therapies.\"},{\"question\":\"What evidence links leptin (LEP) to colorectal cancer liver metastasis?\",\"answer\":\"Integrated bioinformatics linked LEP to CRLM, and functional assays showed LEP overexpression enhanced CRC cell proliferation, invasion, and metastatic potential. In vivo, a CRLM murine model supported LEP involvement in hepatic metastasis and M2 macrophage polarization.\"},{\"question\":\"How does LEP relate to lipid metabolism and immune macrophages in the proposed mechanism?\",\"answer\":\"Lipid staining indicated LEP-associated lipid metabolic alterations. Immunofluorescence, qRT-PCR, and ELISA further supported that LEP correlates with increased M2 macrophage markers and related cytokines, suggesting immunosuppressive polarization contributes to CRLM progression.\"}]","Potential role of leptin in colorectal cancer liver metastasis involving lipid metabolic reprogramming and immunosuppressive macrophage polarization | PDF",1790128413,43]