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Traditional models, relying on single-sample, single-region bulk RNA sequencing, fall short of capturing the complexity of intratumor heterogeneity. To fill this gap, we developed a computational model for intratumor heterogeneity corrected signature (ITHCS) by employing both multiregion bulk and single-cell RNA sequencing to pinpoint genes that exhibit consistent expression patterns across different tumor regions but vary significantly among patients. Utilizing these genes, we applied multiple machine-learning algorithms for sophisticated feature selection and model construction. The ITHCS model significantly outperforms existing prognostic indicators in accuracy and generalizability, markedly reducing sampling biases caused by intratumor heterogeneity. This improvement is especially notable in the prognostic assessment of early-stage ESCC patients, where the model exhibits exceptional predictive power. Additionally, we found that the risk score based on ITHCS may be associated with epithelial-mesenchymal transition characteristics, indicating that high-risk patients may exhibit a diminished efficacy to immunotherapy.<\/jats:p>","DOI":"10.1093\/bib\/bbae631","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T06:06:21Z","timestamp":1734501981000},"source":"Crossref","is-referenced-by-count":2,"title":["A novel computational model ITHCS for enhanced prognostic risk stratification in ESCC by correcting for intratumor heterogeneity"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6259-5070","authenticated-orcid":false,"given":"Tong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , 197 Ruijin 2nd Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Shanghai Institute of Immunology , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Shanghai Jiao Tong University School of Medicine , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7532-2217","authenticated-orcid":false,"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , 197 Ruijin 2nd Road, Huangpu District, Shanghai 200025,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangyang","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , 197 Ruijin 2nd Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Shanghai Institute of Immunology , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Shanghai Jiao Tong University School of Medicine , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyi","family":"Han","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Shanghai Jiao Tong University School of Medicine , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Department of Neurosurgery , Center of Pituitary Tumor, , 197 Ruijin 2nd Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Center of Pituitary Tumor, , 197 Ruijin 2nd Road, Huangpu District, Shanghai 200025,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zizhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine , 639 Zhizaoju Road, Huangpu District, Shanghai 200011,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , 197 Ruijin 2nd Road, Huangpu District, Shanghai 200025,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shugeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-4710","authenticated-orcid":false,"given":"Youqiong","family":"Ye","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]},{"name":"Shanghai Jiao Tong University School of Medicine , State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, , 227 Chongqing South Road, Huangpu District, Shanghai 200025,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hecheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , 197 Ruijin 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