{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:28:44Z","timestamp":1785796124145,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H270007"],"award-info":[{"award-number":["LY21H270007"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Colorectal cancer (CRC) is a fatal malignant tumor with poor prognosis. Cancer stem cells (CSCs) can cause metastasis, recurrence and drug resistance in CRC. This research aimed to analyze stemness\u2010related prognostic genes of CRC based on single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DESeq2 was applied to analyze the differentially expressed genes (DEGs). The mRNA stemness index (mRNAsi) was calculated by one\u2010class logistic regression (OCLR). The stemness\u2010related cells were analyzed based on scRNA\u2010seq dataset GSE166555. Monocle 2 algorithm was used for stemness\u2010related cells pseudotime trajectory analysis. The stemness\u2010related prognostic genes were analyzed by clusterProfiler and survival package. The stemness of CRC cells was detected by spheroid formation assay, and the expression of stemness\u2010related prognostic genes was verified by qRT\u2010PCR and Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>7916 DEGs between the CRC and normal tissues were obtained. The mRNAsi of the CRC tissues was shown to be significantly higher than that of the normal tissues. 7 and 8 cell types were annotated respectively in the normal and CRC tissues through analysis of the scRNA\u2010seq data. Cell\u2013cell interactions (CCIs) in the tumor tissues were revealed to be significantly enhanced than that in the normal tissues. By calculating the \u2018stemness score\u2019, CSCs, epithelial cells (EPCs) and cancer\u2010associated fibroblasts (CAFs) were defined as stemness\u2010related cells. Through pseudotime trajectory analysis, 2111 genes were identified as state 2\u2010specific genes. Then, 41 genes were obtained by taking intersection of the up\u2010regulated genes with state 2\u2010specific genes and marker genes of CSCs, EPCs and CAFs. The univariate COX regression analysis revealed 5 stemness\u2010related prognostic genes (TIMP1, PGF, FSTL3, SNAI1 and FOXC1). Kaplan\u2013Meier curve analysis indicated that the higher the expression of 5 genes, the lower the survival rate. In vitro cell experiment confirmed that the expression of TIMP1, PGF and SNAI1 was consistent with that revealed by bioinformatics analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TIMP1, PGF and SNAI1 were identified as stemness\u2010related prognostic genes of CRC, and possibly potential therapeutic targets for CRC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5833","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T14:10:49Z","timestamp":1680703849000},"page":"11611-11623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Role of stemness\u2010related genes TIMP1, PGF, and SNAI1 in the prognosis of colorectal cancer through single\u2010cell RNA\u2010seq"],"prefix":"10.1002","volume":"12","author":[{"given":"Yan","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tongde Hospital of Zhejiang Province  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1109-3372","authenticated-orcid":false,"given":"Bin","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang 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