{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:02:56Z","timestamp":1779692576904,"version":"3.53.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lynch Syndrome (LS) is an autosomal dominant disease characterized by germline heterozygous mutations in DNA mismatch repair (MMR) genes. High-risk LS patients may proceed to colorectal cancer (CRC). However, the drivers or biomarkers of LS benign colon tissue approaching malignant CRC are not completely understood. This study aimed to understand the molecular and cellular changes during malignant transition in LS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing (scRNA-seq) was used to analyze paired fresh biopsy samples from 3 LS patients (carcinoma vs. para-carcinoma, labeled as LS-CA vs. LS-paraCA). Single-nuclear RNA sequencing (snRNA-seq) was used to analyze a frozen biopsy sample of a LS patient. Datasets of Healthy controls and patients diagnosed with sporadic CRC (without LS-related germline or somatic mutations; labeled as nonLS-CRC) were downloaded from the open source. Integrative computational analysis was performed to conclude potential drivers of the malignant transition. Immuno-histo-fluorescence staining (IHF) were also performed for validating the proposed three key markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the single-cell atlas, we observed an increase of primitive cancer stem-cells with high expression of biomarkers\n                      <jats:italic>CEACAM5, BACE2<\/jats:italic>\n                      ,\n                      <jats:italic>GPRC5A<\/jats:italic>\n                      and\n                      <jats:italic>OLFM4<\/jats:italic>\n                      in the epithelium of the LS. Both infiltration of immune cells and pathways related to DNA repair biological activity in LS are dramatically increased in carcinoma compared to para-carcinoma. The mutation burden in LS is fundamentally elevated compared to that in healthy controls. Furthermore, T cell and macrophage-related tumor immunity in LS is readily mobilized in carcinomas compared to para-carcinoma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides single-cell transcriptomic resource using affected tissues from patients with Lynch Syndrome and describes an integrative profile covering the alterations of cancer stem cell markers, mutation burden, and tumor immunity during the malignant transition from latency state to Lynch Syndrome and to colorectal cancer at the single-cell level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1722806","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:06:07Z","timestamp":1779689167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tracing the stemness and malignant transition in a heritable colorectal cancer Lynch Syndrome by single-cell RNA-seq analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Junfeng","family":"Xu","sequence":"first","affiliation":[{"name":"Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Department of Bioinformatics; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Inflammatory Biology; Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Inflammatory Biology; Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianru","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Seventh Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Seventh Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiu","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Inflammatory Biology; Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Yang","sequence":"additional","affiliation":[{"name":"Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]},{"name":"Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Department of Bioinformatics; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Inflammatory Biology; Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Department of Rheumatology and Immunology, Tianjin Medical University Tianjin General Hospital","place":["Tianjin, China"]},{"name":"Department of Hematology, Tianjin Medical University Tianjin General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21448","article-title":"Recent progress in lynch syndrome and other familial colorectal cancer syndromes","volume":"68","author":"Boland","year":"2018","journal-title":"Ca-A Cancer J For Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0004.2009.01230.x","article-title":"Review of the lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications","volume":"76","author":"Lynch","year":"2009","journal-title":"Clin 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