{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:23:16Z","timestamp":1789024996232,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"publisher","award":["23010902146"],"award-info":[{"award-number":["23010902146"]}],"id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"publisher"}]},{"award":["23010902146"],"award-info":[{"award-number":["23010902146"]}],"id":[{"id":"https:\/\/ror.org\/00engpz63","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Abu Dhabi\u2019s Advanced Technology Research Council","award":["VRI-20\u201310"],"award-info":[{"award-number":["VRI-20\u201310"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor-associated Tie2-expressing monocytes\/macrophages (TEMs) have been implicated in promoting angiogenesis and metastasis in colorectal cancer (CRC), yet the molecular mechanisms linking TEMs infiltration to tumor metastasis and progression remain incompletely defined. This study investigated the distribution of TEMs in CRC and their association with gene expression profiles, microvessel density (MVD), and clinical outcomes. Immunohistochemistry on 30 formalin-fixed paraffin-embedded (FFPE) primary CRC samples revealed that TEMs, which characteristically express tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2) receptor and CD14, preferentially localize to perivascular regions and are associated with higher histological grade, tumor size, lymph node metastasis, and increased MVD. However, Tie2\u2212\/CD14+ macrophages and CD68+ tumor-associated macrophages (TAMs) showed uniform stromal distribution. Gene set enrichment analysis (GSEA) of in silico transcriptomic datasets of metastatic CRC (mCRC) identified enrichment of pathways related to cell\u2013cell recognition, calcium signaling, transcription regulation, and metalloexopeptidase activity in Tie2+\/CD14+ tumors. Subsequent qRT-PCR validation on FFPE primary CRC samples confirmed significant upregulation of C-C chemokine receptor 7 (CCR7), platelet-derived growth factor A (PDGFRA), CBP\/p300-interacting transactivator with glutamic acid\/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), and carboxypeptidase E (CPE) in TEMs+ regions. Notably, angiopoietin1 (Ang1), but not angiopoietin2 (Ang2), was significantly elevated in TEMs+ primary tumors. Kaplan\u2013Meier analysis on 1336 CRC patients indicated that high expression of CITED2, CPE, and Ang2 is associated with reduced overall survival. Collectively, these findings suggest that TEM infiltration is linked to transcriptional regulation, biological processes, and enzymatic programs in CRC, potentially contributing to tumor progression and poor prognosis, and highlight CCR7, PDGFRA, CITED2, CPE, and Ang1 as candidate biomarkers for further mechanistic exploration.<\/jats:p>","DOI":"10.3390\/ijms27083645","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative In Silico and FFPE Tissue Analyses Elucidate Upregulated Genes in Colorectal Cancer Enriched for Tie2-Expressing Macrophages\/Monocytes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3354-4539","authenticated-orcid":false,"given":"Eman Amin M.","family":"Ali","sequence":"first","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-0899","authenticated-orcid":false,"given":"Alaa Muayad","family":"Altaie","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Center of Excellence for Precision Medicine, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2893-2872","authenticated-orcid":false,"given":"Reem Sami","family":"Alhamidi","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nival","family":"Ali","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anania","family":"Boghossian","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Almazrouei","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya Bijosh","family":"Mohan","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5158-4590","authenticated-orcid":false,"given":"Riyad","family":"Bendardaf","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Oncology Department, University Hospital Sharjah, Sharjah P.O. Box 72772, United Arab Emirates"},{"name":"Center of Excellence for Cancer Research, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawia","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Department, Burjeel Medical City, Abu Dhabi P.O. Box 9054, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5259-327X","authenticated-orcid":false,"given":"Iman M.","family":"Talaat","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Pathology Department, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-0868","authenticated-orcid":false,"given":"Rifat","family":"Hamoudi","sequence":"additional","affiliation":[{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Center of Excellence for Precision Medicine, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"Division of Surgery and Interventional Science, University College London, London NW3 2PS, UK"},{"name":"BIMAI-Lab\u2014Biomedically Informed Artificial Intelligence Laboratory, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"},{"name":"ASPIRE Precision Medicine Research Institute Abu Dhabi, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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