{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:01:13Z","timestamp":1782856873876,"version":"3.54.5"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["Nicol\u00e1s Monardes"],"award-info":[{"award-number":["Nicol\u00e1s Monardes"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad de C\u00f3rdoba"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Diagn Ther"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s40291-026-00856-3","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:20:49Z","timestamp":1782066049000},"page":"707-717","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Considering Tumour Sidedness is Critical for Accurate Interpretation of Liquid Biopsy Results in Metastatic Colorectal Cancer"],"prefix":"10.1007","volume":"30","author":[{"given":"Marta","family":"Toledano-Fonseca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ic\u00edar","family":"de la Fuente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Ortiz-Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Cano-Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Pulido-Cortijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Cano-Osuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Victoria","family":"Garc\u00eda-Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Auxiliadora","family":"G\u00f3mez-Espa\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rodr\u00edguez-Ariza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Aranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"856_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/CAAC.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u201363. https:\/\/doi.org\/10.3322\/CAAC.21834.","journal-title":"CA Cancer J Clin"},{"key":"856_CR2","doi-asserted-by":"publisher","DOI":"10.21037\/ATM.2019.07.91","volume":"7","author":"C Mattiuzzi","year":"2019","unstructured":"Mattiuzzi C, Sanchis-Gomar F, Lippi G. Concise update on colorectal cancer epidemiology. Ann Transl Med. 2019;7:609. https:\/\/doi.org\/10.21037\/ATM.2019.07.91.","journal-title":"Ann Transl Med"},{"key":"856_CR3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1159\/000454687","volume":"33","author":"JW Holch","year":"2017","unstructured":"Holch JW, Demmer M, Lamersdorf C, Michl M, Schulz C, Von Einem JC, et al. Pattern and dynamics of distant metastases in metastatic colorectal cancer. Visc Med. 2017;33:70\u20135. https:\/\/doi.org\/10.1159\/000454687.","journal-title":"Visc Med"},{"key":"856_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/SREP29765","volume":"6","author":"M Riihimaki","year":"2016","unstructured":"Riihimaki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765. https:\/\/doi.org\/10.1038\/SREP29765.","journal-title":"Sci Rep"},{"key":"856_CR5","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.ejso.2014.11.001","volume":"41","author":"GH Lee","year":"2015","unstructured":"Lee GH, Malietzis G, Askari A, Bernardo D, Al-Hassi HO, Clark SK. Is right-sided colon cancer different to left-sided colorectal cancer? A systematic review. Eur J Surg Oncol. 2015;41:300\u20138. https:\/\/doi.org\/10.1016\/j.ejso.2014.11.001.","journal-title":"Eur J Surg Oncol"},{"key":"856_CR6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.4251\/WJGO.V12.I4.405","volume":"12","author":"H Aggarwal","year":"2020","unstructured":"Aggarwal H, Sheffield KM, Li L, Lenis D, Sorg R, Barzi A, et al. Primary tumor location and survival in colorectal cancer: a retrospective cohort study. World J Gastrointest Oncol. 2020;12:405\u201323. https:\/\/doi.org\/10.4251\/WJGO.V12.I4.405.","journal-title":"World J Gastrointest Oncol"},{"key":"856_CR7","doi-asserted-by":"publisher","first-page":"264","DOI":"10.14740\/GR1062W","volume":"11","author":"B Baran","year":"2018","unstructured":"Baran B, Mert Ozupek N, Yerli Tetik N, Acar E, Bekcioglu O, Baskin Y. Difference between left-sided and right-sided colorectal cancer: a focused review of literature. Gastroenterol Res. 2018;11:264\u201373. https:\/\/doi.org\/10.14740\/GR1062W.","journal-title":"Gastroenterol Res"},{"key":"856_CR8","doi-asserted-by":"publisher","DOI":"10.1007\/S11864-018-0544-Y","volume":"19","author":"M Ghidini","year":"2018","unstructured":"Ghidini M, Petrelli F, Tomasello G. Right versus left colon cancer: resectable and metastatic disease. Curr Treat Opt Oncol. 2018;19:31. https:\/\/doi.org\/10.1007\/S11864-018-0544-Y.","journal-title":"Curr Treat Opt Oncol"},{"key":"856_CR9","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1002\/CAM4.2747","volume":"9","author":"LC Bylsma","year":"2020","unstructured":"Bylsma LC, Gillezeau C, Garawin TA, Kelsh MA, Fryzek JP, Sangar\u00e9 L, et al. Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: a systematic review and meta-analysis. Cancer Med. 2020;9:1044\u201357. https:\/\/doi.org\/10.1002\/CAM4.2747.","journal-title":"Cancer Med"},{"key":"856_CR10","doi-asserted-by":"publisher","first-page":"411","DOI":"10.6004\/JNCCN.2017.0038","volume":"15","author":"MS Lee","year":"2017","unstructured":"Lee MS, Menter DG, Kopetz S. Right versus left colon cancer biology: integrating the consensus molecular subtypes. J Natl Compr Canc Netw. 2017;15:411\u20139. https:\/\/doi.org\/10.6004\/JNCCN.2017.0038.","journal-title":"J Natl Compr Canc Netw"},{"key":"856_CR11","doi-asserted-by":"publisher","unstructured":"Cremolini C, Chalabi M, Elez E, Fassan M, Gelli M, Go\u00e9r\u00e9 D, et al. Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2026. https:\/\/doi.org\/10.1016\/j.annonc.2026.03.005. (Epub ahead of print).","DOI":"10.1016\/j.annonc.2026.03.005"},{"key":"856_CR12","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines). Colon cancer. Version 2. 2026. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/colon.pdf. Accessed 17 May 2026."},{"key":"856_CR13","doi-asserted-by":"publisher","first-page":"687","DOI":"10.21037\/JGO.2016.06.12","volume":"7","author":"J Gong","year":"2016","unstructured":"Gong J, Cho M, Fakih M. RAS and BRAF in metastatic colorectal cancer management. J Gastrointest Oncol. 2016;7:687\u2013704. https:\/\/doi.org\/10.21037\/JGO.2016.06.12.","journal-title":"J Gastrointest Oncol"},{"key":"856_CR14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/annonc\/mdu378","volume":"26","author":"MJ Sorich","year":"2015","unstructured":"Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol. 2015;26:13\u201321. https:\/\/doi.org\/10.1093\/annonc\/mdu378.","journal-title":"Ann Oncol"},{"key":"856_CR15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/S41576-018-0071-5","volume":"20","author":"E Heitzer","year":"2019","unstructured":"Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20:71\u201388. https:\/\/doi.org\/10.1038\/S41576-018-0071-5.","journal-title":"Nat Rev Genet"},{"key":"856_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0174308","volume":"12","author":"AW Berger","year":"2017","unstructured":"Berger AW, Schwerdel D, Welz H, Marienfeld R, Schmidt SA, Kleger A, et al. Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA. PLoS ONE. 2017;12:e0174308. https:\/\/doi.org\/10.1371\/JOURNAL.PONE.0174308.","journal-title":"PLoS ONE"},{"key":"856_CR17","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1159\/000494411","volume":"99","author":"T Yamada","year":"2018","unstructured":"Yamada T, Matsuda A, Koizumi M, Shinji S, Takahashi G, Iwai T, et al. Liquid biopsy for the management of patients with colorectal cancer. Digestion. 2018;99:39\u201345. https:\/\/doi.org\/10.1159\/000494411.","journal-title":"Digestion"},{"key":"856_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS19113356","volume":"19","author":"V Vymetalkova","year":"2018","unstructured":"Vymetalkova V, Cervena K, Bartu L, Vodicka P. Circulating cell-free DNA and colorectal cancer: a systematic review. Int J Mol Sci. 2018;19:3356. https:\/\/doi.org\/10.3390\/IJMS19113356.","journal-title":"Int J Mol Sci"},{"key":"856_CR19","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1634\/THEONCOLOGIST.2016-0178","volume":"22","author":"K-LG Spindler","year":"2017","unstructured":"Spindler K-LG, Boysen AK, Pallisg\u00e5rd N, Johansen JS, Tabernero J, S\u00f8rensen MM, et al. Cell-free DNA in metastatic colorectal cancer: a systematic review and meta-analysis. Oncologist. 2017;22:1049\u201355. https:\/\/doi.org\/10.1634\/THEONCOLOGIST.2016-0178.","journal-title":"Oncologist"},{"key":"856_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-019-45616-Y","volume":"9","author":"A Vivancos","year":"2019","unstructured":"Vivancos A, Aranda E, Benavides M, \u00c9lez E, G\u00f3mez-Espa\u00f1a MA, Toledano M, et al. Comparison of the clinical sensitivity of the Idylla Platform and the OncoBEAM RAS CRC assay for KRAS mutation detection in liquid biopsy samples. Sci Rep. 2019;9:8976. https:\/\/doi.org\/10.1038\/S41598-019-45616-Y.","journal-title":"Sci Rep"},{"key":"856_CR21","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1007\/S12094-024-03801-0","volume":"27","author":"E Gonz\u00e1lez-Flores","year":"2025","unstructured":"Gonz\u00e1lez-Flores E, Garcia-Carbonero R, \u00c9lez E, Redondo-Cerezo E, Safont MJ, Vera Garc\u00eda R. Gender and sex differences in colorectal cancer screening, diagnosis and treatment. Clin Transl Oncol. 2025;27:2825\u201337. https:\/\/doi.org\/10.1007\/S12094-024-03801-0.","journal-title":"Clin Transl Oncol"},{"key":"856_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.101204","volume":"8","author":"I Baraibar","year":"2023","unstructured":"Baraibar I, Ros J, Saoudi N, Salv\u00e0 F, Garc\u00eda A, Castells MR, et al. Sex and gender perspectives in colorectal cancer. ESMO Open. 2023;8:101204. https:\/\/doi.org\/10.1016\/j.esmoop.2023.101204.","journal-title":"ESMO Open"},{"key":"856_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/S10151-020-02329-Z","volume":"25","author":"RT de Paula","year":"2021","unstructured":"de Paula RT, Simon HL, da Luz PMM, Keller DS. Right sided colorectal cancer increases with age and screening should be tailored to reflect this: a national cancer database study. Tech Coloproctol. 2021;25:81\u20139. https:\/\/doi.org\/10.1007\/S10151-020-02329-Z.","journal-title":"Tech Coloproctol"},{"key":"856_CR24","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1159\/000510944","volume":"99","author":"G De Renzi","year":"2021","unstructured":"De Renzi G, Gaballo G, Gazzaniga P, Nicolazzo C. Molecular biomarkers according to primary tumor location in colorectal cancer: current standard and new insights. Oncology. 2021;99:135\u201343. https:\/\/doi.org\/10.1159\/000510944.","journal-title":"Oncology"},{"key":"856_CR25","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/annonc\/mdz139","volume":"30","author":"J Hamfjord","year":"2019","unstructured":"Hamfjord J, Guren TK, Dajani O, Johansen JS, Glimelius B, Sorbye H, et al. Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy. Ann Oncol. 2019;30:1088\u201395. https:\/\/doi.org\/10.1093\/annonc\/mdz139.","journal-title":"Ann Oncol"},{"key":"856_CR26","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1158\/1535-7163.MCT-15-0820","volume":"15","author":"D Azuara","year":"2016","unstructured":"Azuara D, Santos C, Lopez-Doriga A, Grasselli J, Nadal M, Sanjuan X, et al. Nanofluidic digital PCR and extended genotyping of RAS and BRAF for improved selection of metastatic colorectal cancer patients for anti-EGFR therapies. Mol Cancer Ther. 2016;15:1106\u201312. https:\/\/doi.org\/10.1158\/1535-7163.MCT-15-0820.","journal-title":"Mol Cancer Ther"},{"key":"856_CR27","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1158\/1078-0432.CCR-14-0983","volume":"21","author":"P Laurent-Puig","year":"2015","unstructured":"Laurent-Puig P, Pekin D, Normand C, Kotsopoulos SK, Nizard P, Perez-Toralla K, et al. Clinical relevance of KRAS-mutated subclones detected with picodroplet digital PCR in advanced colorectal cancer treated with anti-EGFR therapy. Clin Cancer Res. 2015;21:1087\u201397. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-0983.","journal-title":"Clin Cancer Res"},{"key":"856_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S12943-025-02327-5","volume":"24","author":"HJ Boka","year":"2025","unstructured":"Boka HJ, Engel RM, Georges C, McMurrick PJ, Abud HE. Does side matter? Deciphering mechanisms that underpin side-dependent pathogenesis and therapy response in colorectal cancer. Mol Cancer. 2025;24:1\u201314. https:\/\/doi.org\/10.1186\/S12943-025-02327-5.","journal-title":"Mol Cancer"},{"key":"856_CR29","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.trsl.2024.12.002","volume":"276","author":"C Hu","year":"2025","unstructured":"Hu C, Huang X, Chen J, Liang W, Yang K, Jiang H, et al. Dissecting the cellular reprogramming and tumor microenvironment in left- and right-sided colorectal cancer by single cell RNA sequencing. Transl Res. 2025;276:22\u201337. https:\/\/doi.org\/10.1016\/j.trsl.2024.12.002.","journal-title":"Transl Res"}],"container-title":["Molecular Diagnosis &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-026-00856-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40291-026-00856-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-026-00856-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:57:17Z","timestamp":1782853037000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40291-026-00856-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,21]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["856"],"URL":"https:\/\/doi.org\/10.1007\/s40291-026-00856-3","relation":{},"ISSN":["1177-1062","1179-2000"],"issn-type":[{"value":"1177-1062","type":"print"},{"value":"1179-2000","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,21]]},"assertion":[{"value":"5 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was funded by Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CB16\/12\/00349). Antonio Rodr\u00edguez-Ariza and Mar\u00eda Victoria Garc\u00eda-Ortiz are funded with a researcher contract through the programme \u201cNicol\u00e1s Monardes\u201d from Junta de Andaluc\u00eda.\u00a0Funding for open access charge: Universidad de C\u00f3rdoba \/ CBUA.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Marta Toledano-Fonseca, Ic\u00edar de la Fuente, Mar\u00eda Jos\u00e9 Ortiz-Morales, Pablo Cano-Ram\u00edrez, Gema Pulido-Cortijo, Mar\u00eda Teresa Cano-Osuna, Mar\u00eda Victoria Garc\u00eda-Ortiz, Mar\u00eda Auxiliadora G\u00f3mez-Espa\u00f1a, Antonio Rodr\u00edguez-Ariza and Enrique Aranda have no conflicts of interest that are directly relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki, and the protocol (FCO-BIOPLIQ2015) was approved by the Ethics Committee of C\u00f3rdoba.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients gave their informed consent for their inclusion.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Data are available on request from the authors.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"MT-F and IF: methodology, investigation, formal analysis, writing (original draft preparation). MJO-M, GP-C, MTC-O: resources. PC-R, MVG-O: investigation. MAG-E: resources, writing (review and editing). AR-A: conceptualization, supervision, writing (review and editing). EA: conceptualization, supervision, writing (review and editing), funding acquisition. All authors have read and approved the final version.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}