{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T08:08:33Z","timestamp":1762848513101,"version":"build-2065373602"},"reference-count":19,"publisher":"Aboutscience Srl","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Circ Biomark"],"abstract":"<jats:p>Introduction: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) may be considered aneffective option in the neoadjuvant setting for metastatic colon cancer (mCRC). To investigate potential molecularcriteria for treatment response, we evaluate the transcriptome of paired primary colon tumors and livermetastases.Method: Two sets of quadruple-matched specimens (primary colon tumor, liver metastasis, normal colon andliver tissues) from five patients with resectable mCRC before and after neoadjuvant FOLFOXIRI were selected forRNA sequencing (RNA-seq).Results: RNA-seq data showed that liver metastases exhibited a higher number of differentially expressed genes(DEGs) than colon tumors (FDR &lt; 0.05, 301 vs. 62, respectively). Up-regulation of IL1RN, MTCO1P12, RN7SL1,ALDH1A1, DUSP1, COX1, and FOS may be associated with colon tumor sensitivity to FOLFOXIRI. HBB, GADD45B,DUSP1, FOSB, HBA2, TSC22D3, TAGLN, PER1, CSRP1, CCN2, NAMPT, ZBTB16, SERPINE1, ISG20, SRGN, ATF3, IL7R,IFITM2, and KLF2 may potentially be involved in the partial liver metastasis response. EPS8L2 was the only genehighly expressed in pre-treatment liver tissue of the complete responder patient compared to others (|Log2FC|= 3.84, FDR &lt; 0.05).Conclusion: Data obtained indicate transcriptional discordance between the primary tumors and liver metastasesduring neoadjuvant FOLFOXIRI, with the pattern of DEGs involved in their response being distinct. The EPS8L2transcript could be regarded as a candidate biomarker of liver complete response; however, prognostic conclusionscannot be drawn from this cohort.<\/jats:p>","DOI":"10.33393\/jcb.2025.3597","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T08:05:14Z","timestamp":1762848314000},"page":"48-53","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptome biomarkers of colon cancer liver metastasis response to neoadjuvant triplet chemotherapy: a case series"],"prefix":"10.33393","volume":"14","author":[{"given":"Nataliya","family":"Babyshkina","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Dronova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Eremin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Dobrodeev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Kostromitskiy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Vtorushin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polina","family":"Gervas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Afanasiev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadejda","family":"Cherdyntseva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"18642","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"17931","doi-asserted-by":"crossref","unstructured":"Benson AB, Venook AP, Al-Hawary MM, et al. Colon Cancer, Version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(3):329-359. https:\/\/doi.org\/10.6004\/jnccn.2021.0012 PMID:33724754","DOI":"10.6004\/jnccn.2021.0012"},{"key":"17932","doi-asserted-by":"crossref","unstructured":"Vatandoust S, Price TJ, Karapetis CS. Colorectal cancer: metastases to a single organ. World J Gastroenterol. 2015;21(41):11767\u201311776. https:\/\/doi.org\/10.3748\/wjg.v21.i41.11767.","DOI":"10.3748\/wjg.v21.i41.11767"},{"key":"17933","doi-asserted-by":"crossref","unstructured":"Cervantes A, Adam R, Rosell\u00f3 S, et al.; ESMO Guidelines Committee. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(1):10-32. https:\/\/doi.org\/10.1016\/j.annonc.2022.10.003 PMID:36307056","DOI":"10.1016\/j.annonc.2022.10.003"},{"key":"17934","doi-asserted-by":"crossref","unstructured":"Falcone A, Ricci S, Brunetti I, et al.; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670-1676. https:\/\/doi.org\/10.1200\/JCO.2006.09.0928 PMID:17470860","DOI":"10.1200\/JCO.2006.09.0928"},{"key":"17935","doi-asserted-by":"crossref","unstructured":"Masi G, Vasile E, Loupakis F, et al. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst. 2011;103(1):21-30. https:\/\/doi.org\/10.1093\/jnci\/djq456 PMID:21123833","DOI":"10.1093\/jnci\/djq456"},{"key":"17936","doi-asserted-by":"crossref","unstructured":"Zhang W, Zhou H, Jiang J, et al. Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer to transform effectively EMVI and MRF from positive to negative: results of a long-term single center phase 2 clinical trial. BMC Cancer. 2023;23(1):592. https:\/\/doi.org\/10.1186\/s12885-023-11103-x PMID:37370032","DOI":"10.1186\/s12885-023-11103-x"},{"key":"17937","doi-asserted-by":"crossref","unstructured":"Bond MJG, Bolhuis K, Loosveld OJL, et al.; Dutch Colorectal Cancer Study Group. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomized, controlled, phase 3 study from the Dutch Colorectal Cancer Group. Lancet Oncol. 2023;24(7):757-771. https:\/\/doi.org\/10.1016\/S1470-2045(23)00219-X PMID:37329889","DOI":"10.1016\/j.hpb.2023.07.006"},{"key":"17938","doi-asserted-by":"crossref","unstructured":"Cremolini C, Antoniotti C, Rossini D, et al.; GONO Foundation Investigators. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomized, controlled trial. Lancet Oncol. 2020;21(4):497-507. https:\/\/doi.org\/10.1016\/S1470-2045(19)30862-9 PMID:32164906","DOI":"10.2139\/ssrn.3478102"},{"key":"17939","doi-asserted-by":"crossref","unstructured":"Hu H, Wang K, Huang M, et al. Modified FOLFOXIRI with or without cetuximab as conversion therapy in patients with RAS\/BRAF wildtype unresectable liver metastases colorectal cancer: the FOCULM multicenter phase II trial. Oncologist. 2021;26(1):e90-e98. https:\/\/doi.org\/10.1634\/theoncologist.2020-0563 PMID:33400355","DOI":"10.1634\/theoncologist.2020-0563"},{"key":"17940","doi-asserted-by":"crossref","unstructured":"Folprecht G, Martinelli E, Mazard T, et al. Triplet chemotherapy in combination with anti-EGFR agents for the treatment of metastatic colorectal cancer: current evidence, advances, and future perspectives. Cancer Treat Rev. 2022;102:102301. https:\/\/doi.org\/10.1016\/j.ctrv.2021.102301 PMID:34839118","DOI":"10.1016\/j.ctrv.2021.102301"},{"key":"17941","doi-asserted-by":"crossref","unstructured":"Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680-2686. https:\/\/doi.org\/10.1002\/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C PMID:8194005","DOI":"10.1002\/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C"},{"key":"17942","doi-asserted-by":"crossref","unstructured":"Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. 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Comparative sequence analysis of patient-matched primary colorectal cancer, metastatic, and recurrent metastatic tumors after adjuvant FOLFOX chemotherapy. BMC Cancer. 2019;19(1):255. https:\/\/doi.org\/10.1186\/s12885-019-5479-6 PMID:30898102","DOI":"10.1186\/s12885-019-5479-6"},{"key":"17946","doi-asserted-by":"crossref","unstructured":"Calero-Cuenca FJ, Osorio DS, Carvalho-Marques S, et al. Ctdnep1 and Eps8L2 regulate dorsal actin cables for nuclear positioning during cell migration. Curr Biol. 2021;31(7):1521-1530.e8. https:\/\/doi.org\/10.1016\/j.cub.2021.01.007 PMID:33567288","DOI":"10.1016\/j.cub.2021.01.007"},{"key":"17947","doi-asserted-by":"crossref","unstructured":"Luo K, Zhang L, Liao Y, et al. Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review). [Review]. Oncol Rep. 2021;45(3):824-834. https:\/\/doi.org\/10.3892\/or.2021.7927 PMID:33432368","DOI":"10.3892\/or.2021.7927"},{"key":"17948","doi-asserted-by":"crossref","unstructured":"Huang R, Liu H, Chen Y, et al. EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL\/PI3K\/AKT\/mTOR pathway. Oncol Rep. 2018;39(1):119-128. https:\/\/doi.org\/10.3892\/or.2017.6102 PMID:29192326","DOI":"10.3892\/or.2017.6102"},{"key":"17949","doi-asserted-by":"crossref","unstructured":"Gorsic LK, Stark AL, Wheeler HE, et al. EPS8 inhibition increases cisplatin sensitivity in lung cancer cells. 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