{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:19:08Z","timestamp":1787663948234,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To validate c\u2010MET protein expression in colorectal cancer (CRC) and assess whether joint MET and hepatocyte growth factor (HGF) transcript expression provides descriptive information on tumor microenvironment features beyond MET alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>c\u2010MET protein expression was evaluated by immunohistochemistry in 51 paired CRC and adjacent tissues. The Cancer Genome Atlas (TCGA) and TNMplot datasets assessed MET mRNA expression and clinicopathological associations; Kaplan\u2013Meier Plotter evaluated unadjusted survival; and TIMER (Tumor Immune Estimation Resource) examined purity\u2010adjusted immune correlations. In TCGA colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) cohorts, samples were divided using cohort\u2010specific median MET and HGF expression. ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) and CIBERSORT (Cell\u2010type Identification by Estimating Relative Subsets of RNA Transcripts) compared inferred tumor purity, immune\/stromal scores, and immune\u2010cell composition. These computational estimates were not experimentally validated in this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MET mRNA was elevated in CRC datasets, and c\u2010MET protein H\u2010scores were higher in CRC than in paired adjacent tissues. MET expression was not associated with the tested clinicopathological variables. High MET expression was associated with shorter overall and relapse\u2010free survival in unadjusted analyzes. In both cohorts, the MET\u2010high\/HGF\u2010low group generally showed higher estimated tumor purity and lower immune and stromal scores, whereas the MET\u2010low\/HGF\u2010high group showed the converse pattern. Individual immune\u2010cell subset differences were cohort dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MET mRNA and c\u2010MET protein are elevated in CRC. Joint MET\/HGF expression may complement MET\u2010only analysis by retaining discordant patterns associated with inferred tumor\u2010cell and immune\/stromal composition. These retrospective, algorithm\u2010derived findings do not establish independent prognostic value, HGF\/c\u2010MET pathway activation or causality, or a basis for clinical patient stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72214","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:46:16Z","timestamp":1787636776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Combined MET\/HGF Expression With the Colorectal Cancer Immune Microenvironment: An Integrated Immunohistochemical and Multi\u2010Database Analysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7224-9296","authenticated-orcid":false,"given":"Shuai","family":"Luo","sequence":"first","affiliation":[{"name":"The First Hospital of Tsinghua University, School of Clinical Medicine, Tsinghua Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Guo","sequence":"additional","affiliation":[{"name":"The First Hospital of Tsinghua University, School of Clinical Medicine, Tsinghua Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9547-6793","authenticated-orcid":false,"given":"Xiangli","family":"Li","sequence":"additional","affiliation":[{"name":"The First Hospital of Tsinghua University, School of Clinical Medicine, Tsinghua Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5773-2815","authenticated-orcid":false,"given":"Yiyan","family":"Long","sequence":"additional","affiliation":[{"name":"The First Hospital of Tsinghua University, School of Clinical Medicine, Tsinghua Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zepeng","family":"Xin","sequence":"additional","affiliation":[{"name":"The First Hospital of Tsinghua University, School of Clinical Medicine, Tsinghua Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Cheng","sequence":"additional","affiliation":[{"name":"The First Hospital of Tsinghua University, School of Clinical Medicine, Tsinghua Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2024.01.006"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaf209"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60121951"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010018\u20100002\u2010y"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758834011422556"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010020\u201001711\u2010x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2063"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2018.02.013"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010013\u20100546\u20103"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100014\u2010x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113153"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11252"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052622"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3612"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.2196\/27633"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12395"},{"issue":"11","key":"e_1_2_12_21_1","first-page":"4807","article-title":"MET Is Highly Expressed in Advanced Stages of Colorectal Cancer and Indicates Worse Prognosis and Mortality","volume":"29","author":"Oliveira A. 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