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Current diagnosis depends largely on melanin visualization, yet research on melanosome biogenesis has not produced dependable tools to separate atypical benign, amelanotic, and melanotic lesions. The endosomal-lysosomal system regulates cancer cell biology and melanosome biogenesis. Using pooled secondary analysis of existing gene expression datasets, dysregulated endosomal-lysosomal genes were identified and functionally connected. Immunohistochemistry on patient samples supported candidate protein markers, showing Syntenin-1, Sortilin, and Rab25 distinguish cutaneous melanoma from squamous cell carcinoma, while IGF2R may signal malignant propensity.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/altered-endosomal-lysosomal-biogenesis-in-melanoma-research-article/381491/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/altered-endosomal-lysosomal-biogenesis-in-melanoma-research-article/381491.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is early detection of cutaneous melanoma important?","Question",{"text":113,"@type":114},"Because delayed diagnosis can allow stage progression and markedly reduce 5-year survival, while over-diagnosis of benign lesions also harms patients and healthcare systems.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is the role of the endosomal-lysosomal system in melanoma?",{"text":118,"@type":114},"It regulates cancer cell biology and is involved in melanosome biogenesis, with melanoma cells modifying this system to support viability and promote proliferation, migration, and invasion.",{"name":120,"@type":111,"acceptedAnswer":121},"Which biomarkers does the study suggest for distinguishing melanoma from other skin cancers?",{"text":122,"@type":114},"Dysregulated Syntenin-1, Sortilin, and Rab25 may differentiate cutaneous melanoma from squamous cell carcinoma, while IGF2R may indicate malignant propensity.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},381491,1790480244,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Neoplasia 43 (2023) 100924  \nContents lists available at ScienceDirect  \nNeoplasia  \njournal [homepage:](homepage: www.elsevier.com/locate/neo)[ www.elsevier.com/locate/neo](homepage: www.elsevier.com/locate/neo)  \n| Original Research\u003Cbr>Altered endosomal-lysosomal biogenesis in melanoma |  |  | |\n| --- | --- | --- | --- |\n| Giang T. Lama, Alexandra Sorvinaa, Carmela Martinia, Sarita Prabhakaran b, Ben S.-Y. Unga, Joanna Lazniewska a, Courtney R. Moorea, Andrew R. Beck a, Ashley M. Hopkins c,\u003Cbr>Ian R.D. Johnson a, Maria C. Caruso a, Shane M. Hickey a, Robert D. Brooks a, Louise Jackette, Litsa Karageorgosa, Erwin J. Foster-Smith f, Victoria Malone g, Sonja Klebeb, d, John J. O’Leary g, Douglas A. Brooks a, 1, Jessica M. Logana, 1, *\u003Cbr>a Clinical and Health Sciences, Cancer Research Institute, University of South Australia, Adelaide, SA, Australia b Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia c College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia\u003Cbr>d Department of Surgical Pathology, SA Pathology at Flinders Medical Centre, Adelaide, SA, Australia e Anatomical Pathology Department, Austin Hospital, Melbourne, Vic, Australia\u003Cbr>f Royal Adelaide Hospital, Adelaide, SA, Australia\u003Cbr>g Department of Histopathology, Trinity College Dublin, Ireland |  |  |  |\n| A R T I C L E I N F O |  | A B S T R A C T |  |\n| Keywords:\u003Cbr>Melanoma pathogenesis Endosomal-lysosomal biogenesis Syntenin-1\u003Cbr>Sortilin IGF2R Rab25 |  | Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded technology that can reliably distinguish between atypical benign, amelanotic and melanotic lesions. The endosomal-lysosomal system has important regulatory roles in cancer cell biology, including a specific functional role in melanosome biogenesis. Herein, the involvement of the endosomal-lysosomal system in melanoma was examined by pooled secondary analysis of existing gene expression datasets. A set of differentially expressed endosomal-lysosomal genes was identified in melanoma, which were interconnected by biological function. To illustrate the protein expression of the dysregulated genes, immunohistochemistry was performed on samples from patients with cutaneous melanoma to reveal candidate markers. This study demonstrated the dysregulation of Syntenin-1, Sortilin and Rab25 may provide a differentiating feature between cutaneous melanoma and squamous cell carcinoma, while IGF2R may indicate malignant propensity in these skin cancers. |  |\n\nIntroduction  \nMelanoma results from the malignant transformation of melanocytes, and it is a tumour characterised by marked morphological heterogeneity and high metastatic propensity [1]. The global incidence of melanoma is steadily increasing, with the highest national rates occurring in Australia and New Zealand (approximately 36 cases per 100,000 people diagnosed each year) [2]. Despite significant efforts to improve the detection rates of melanoma, some patients may initially be under-diagnosed as having a benign neoplasm, either clinically and/or histopathologically [3]. A delayed diagnosis can result in melanoma stage progression and hindered treatment intervention, drastically  \nreducing individual patient 5-year survival rates (99% at stage I versus 26% at stage IV) [3]. In addition, over-diagnosis of benign melanocytic lesions as melanoma also has important consequences for both patients and healthcare systems, reinforcing the importance of an early accurate diagnosis.  \nAfter clinical assessment, melanoma diagnosis is reliant on histopathological analysis as the current gold standard, although this may be subjective and certain types of lesions can be prone to diagnostic","cbCaigFFJ2EQiNav","https://ap.wps.com/l/cbCaigFFJ2EQiNav","pdf",24119064,"English","# Introduction\n## Melanoma burden and diagnostic challenges\n## Histopathology limitations and need for new technologies\n# Endosomal-lysosomal system in melanoma","[{\"question\":\"Why is early detection of cutaneous melanoma important?\",\"answer\":\"Because delayed diagnosis can allow stage progression and markedly reduce 5-year survival, while over-diagnosis of benign lesions also harms patients and healthcare systems.\"},{\"question\":\"What is the role of the endosomal-lysosomal system in melanoma?\",\"answer\":\"It regulates cancer cell biology and is involved in melanosome biogenesis, with melanoma cells modifying this system to support viability and promote proliferation, migration, and invasion.\"},{\"question\":\"Which biomarkers does the study suggest for distinguishing melanoma from other skin cancers?\",\"answer\":\"Dysregulated Syntenin-1, Sortilin, and Rab25 may differentiate cutaneous melanoma from squamous cell carcinoma, while IGF2R may indicate malignant propensity.\"}]","Altered endosomal-lysosomal biogenesis in melanoma - research article | PDF",1790245496,25]