{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T22:13:32Z","timestamp":1774995212070,"version":"3.50.1"},"reference-count":140,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ20H160043"],"award-info":[{"award-number":["LQ20H160043"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Fund Project of Zhejiang Medical Association","award":["2019ZYC-A83"],"award-info":[{"award-number":["2019ZYC-A83"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303950"],"award-info":[{"award-number":["82303950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.<\/jats:p>","DOI":"10.1093\/bib\/bbae028","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T07:59:38Z","timestamp":1707724778000},"source":"Crossref","is-referenced-by-count":23,"title":["New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1561-0031","authenticated-orcid":false,"given":"Wenyuan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Yiran","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology , The First Affiliated Hospital, College of Medicine, , Hangzhou, Zhejiang , China"},{"name":"Zhejiang University , The First Affiliated Hospital, College of Medicine, , Hangzhou, Zhejiang , China"}]},{"given":"Hongxia","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University , Haining , China"}]},{"given":"Junjie","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology , Affiliated Hangzhou First People's Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , Affiliated Hangzhou First People's Hospital, , Hangzhou , China"}]},{"given":"Bang","family":"Du","sequence":"additional","affiliation":[{"name":"Real Doctor AI Research Centre , School of Medicine, , Hangzhou 310058 , China"},{"name":"Zhejiang University , School of Medicine, , Hangzhou 310058 , China"}]},{"given":"Mingyu","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Xiaolu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Xiaoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Lili","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Xinhui","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Xuanwen","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-724X","authenticated-orcid":false,"given":"Yifei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , the First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , the First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Nong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Jian","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"given":"Haiping","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-9246","authenticated-orcid":false,"given":"Yongfeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology , The First Affiliated Hospital, , Hangzhou , China"},{"name":"Zhejiang University School of Medicine , The First Affiliated Hospital, , Hangzhou , China"}]}],"member":"286","published-online":{"date-parts":[[2024,2,11]]},"reference":[{"issue":"Suppl 5","key":"2024021207592871100_ref1","doi-asserted-by":"crossref","first-page":"v133","DOI":"10.1093\/annonc\/mdv305","article-title":"Cancers of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"26","author":"Fizazi","year":"2015","journal-title":"Ann 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cancer of unknown primary site","volume":"37","author":"Hayashi","year":"2019","journal-title":"J Clin Oncol"},{"key":"2024021207592871100_ref52","first-page":"6653793","article-title":"Identification of tumor tissue of origin with RNA-Seq data and using gradient boosting strategy","volume":"2021","author":"Li","year":"2021","journal-title":"Biomed Res Int"},{"key":"2024021207592871100_ref53","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1093\/bib\/bbaa031","article-title":"TOD-CUP: a gene expression rank-based majority vote algorithm for tissue origin diagnosis of cancers of unknown primary","volume":"22","author":"Shen","year":"2021","journal-title":"Brief Bioinform"},{"key":"2024021207592871100_ref54","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.jmoldx.2021.07.009","article-title":"Identification of tissue of origin and guided therapeutic applications in cancers of unknown primary using deep learning and RNA sequencing 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