{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:02:32Z","timestamp":1784908952823,"version":"3.55.0"},"reference-count":33,"publisher":"Bioscientifica","issue":"7","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82203684"],"award-info":[{"award-number":["82203684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Papillary thyroid carcinoma (PTC) shows heterogeneous clinical behavior, and current clinicopathologic factors do not fully capture epithelial aggressiveness or tumor microenvironment (TME) remodeling. We integrated single-cell RNA sequencing (scRNA-seq) datasets from normal thyroid tissue, primary PTC, and lymph-node metastases to construct a cross-stage cellular atlas and to characterize epithelial and T\/NK cell heterogeneity. Guided by the malignant epithelial program identified at single-cell resolution, we developed a four-gene risk signature in the TCGA-THCA cohort using Cox and LASSO regression. We further evaluated pathway activity, immune and stromal features, T cell receptor (TCR) diversity, and exploratory in silico drug-response patterns, and we performed small interfering RNA (siRNA)-mediated knockdown of TMEM45A and STC1 in PTC cell lines. The integrated atlas revealed stage-related remodeling of epithelial, immune, and stromal compartments and identified a malignant epithelial state enriched for proliferation-, stress-, and migration-related programs. The four-gene signature was associated with overall survival stratification in TCGA-THCA after adjustment for age, sex, and stage. The high-risk group showed reduced immune infiltration, stronger stromal and epithelial\u2013mesenchymal transition (EMT) signals, lower TCR diversity, and distinct predicted drug-response patterns. In vitro, TMEM45A or STC1 silencing suppressed proliferation and migration and altered EMT-related markers in PTC cells. These findings indicate that a malignant epithelial program defined by single-cell analysis can be translated into a four-gene signature associated with epithelial aggressiveness and TME remodeling in PTC, although its clinical utility requires validation in independent cohorts.<\/jats:p>","DOI":"10.1530\/erc-25-0515","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:48:07Z","timestamp":1783604887000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["Developing an epithelial signature for prognosis of papillary thyroid carcinoma"],"prefix":"10.1530","volume":"33","author":[{"given":"Ziyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Cancer Center, Shenzhen University of Advanced Technology General Hospital 1 , , ,","place":["Shenzhen, Guangdong, 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Institute, OmixScience Co., Ltd 3 , , ,","place":["Shenzhen, Guangdong, China"]},{"name":"OmixScience Laboratory, OmixScience Co., Ltd 4 , , ,","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanchen","family":"Zhao","sequence":"additional","affiliation":[{"name":"OmixScience Research Institute, OmixScience Co., Ltd 3 , , ,","place":["Shenzhen, Guangdong, China"]},{"name":"OmixScience Laboratory, OmixScience Co., Ltd 4 , , ,","place":["Hangzhou, Zhejiang, China"]},{"name":"The Second Affiliated Hospital, Nanjing Medical University 5 , , ,","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglin","family":"Wang","sequence":"additional","affiliation":[{"name":"OmixScience Research Institute, OmixScience Co., Ltd 3 , , ,","place":["Shenzhen, Guangdong, China"]},{"name":"OmixScience Laboratory, OmixScience Co., Ltd 4 , , ,","place":["Hangzhou, Zhejiang, 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