{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:19:45Z","timestamp":1784132385959,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prisma Health transformative seed grant","award":["P20GM109091"],"award-info":[{"award-number":["P20GM109091"]}]},{"name":"2022 ASPIREinG seed grant from the USC School of Medicine Greenville","award":["P20GM109091"],"award-info":[{"award-number":["P20GM109091"]}]},{"name":"Brown SPRINT LINK Award from Brown University","award":["P20GM109091"],"award-info":[{"award-number":["P20GM109091"]}]},{"name":"Functional Genomics Core of the COBRE Center","award":["P20GM109091"],"award-info":[{"award-number":["P20GM109091"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute\u2019s Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients\u2019 sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (\u03b1=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.<\/jats:p>","DOI":"10.3390\/genes15060818","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:33:28Z","timestamp":1718948008000},"page":"818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0554-8157","authenticated-orcid":false,"given":"Ella","family":"Markalunas","sequence":"first","affiliation":[{"name":"Department of Public Health, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-7683","authenticated-orcid":false,"given":"Avery","family":"Funkhouser","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-4994","authenticated-orcid":false,"given":"Julie","family":"Martin","sequence":"additional","affiliation":[{"name":"Prisma Health Cancer Institute, Prisma Health, Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-3226","authenticated-orcid":false,"given":"Michael","family":"Shtutman","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, University of South Carolina College of Pharmacy, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8232-2318","authenticated-orcid":false,"given":"W.","family":"Edenfield","sequence":"additional","affiliation":[{"name":"Prisma Health Cancer Institute, Prisma Health, Greenville, SC 29605, USA"},{"name":"Department of Medicine, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-3120","authenticated-orcid":false,"given":"Anna","family":"Blenda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, SC 29605, USA"},{"name":"Prisma Health Cancer Institute, Prisma Health, Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/annonc\/mdv022","article-title":"Genetics of breast cancer: A topic in evolution","volume":"26","author":"Shiovitz","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cytogfr.2021.03.004","article-title":"Galectins as modulators of receptor tyrosine kinases signaling in health and disease","volume":"60","author":"Matynia","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12943-018-0782-4","article-title":"Mechanisms of receptor tyrosine kinase activation in cancer","volume":"17","author":"Du","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Burguin, A., Diorio, C., and Durocher, F. (2021). Breast cancer treatments: Updates and new challenges. J. Pers. Med., 11.","DOI":"10.3390\/jpm11080808"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chou, F.C., Chen, H.Y., Kuo, C.C., and Sytwu, H.K. (2018). Role of galectins in tumors and in clinical immunotherapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020430"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1158\/0008-5472.CAN-12-2418","article-title":"Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease","volume":"73","author":"Croci","year":"2013","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11006","DOI":"10.1038\/s41598-017-11212-1","article-title":"Glycosylation-dependent galectin-1\/neuropilin-1 interactions promote liver fibrosis through activation of TGF-\u03b2- and PDGF-like signals in hepatic stellate cells","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S0002-9440(10)61780-4","article-title":"Galectin-3 protects human breast carcinoma cells against nitric oxide-induced apoptosis: Implication of galectin-3 function during metastasis","volume":"159","author":"Moon","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, H., Luo, M., Liang, X., Wang, D., Gu, X., Duan, C., Gu, H., Chen, G., Zhao, X., and Zhao, Z. (2014). Galectin-3 as a marker and potential therapeutic target in breast cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103482"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"32940","DOI":"10.1074\/jbc.M112.353334","article-title":"Galectin-3 protein regulates mobility of N-cadherin and GM1 ganglioside at cell-cell junctions of mammary carcinoma cells","volume":"287","author":"Boscher","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3892\/or.2021.8056","article-title":"Galectin-9 suppresses the tumor growth of colon cancer in vitro and in vivo","volume":"45","author":"Morishita","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/ni1271","article-title":"The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity","volume":"6","author":"Zhu","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, D., Zhu, H., and Li, C. (2023). Galectins and galectin-mediated autophagy regulation: New insights into targeted cancer therapy. Biomark. Res., 11.","DOI":"10.1186\/s40364-023-00466-9"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10456-011-9213-5","article-title":"Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress","volume":"14","author":"Ito","year":"2011","journal-title":"Angiogenesis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1080\/13543776.2021.1903430","article-title":"An updated patent review of galectin-1 and galectin-3 inhibitors and their potential therapeutic applications (2016-present)","volume":"31","author":"Sethi","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1158\/1538-7445.AM2020-4918","article-title":"Abstract 4918: Modified citrus pectin slows migration of triple negative breast cancer cells in an impedance-based scratch assay","volume":"80","author":"Zhu","year":"2020","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e154943","DOI":"10.1172\/JCI154943","article-title":"Targeting mutations in cancer","volume":"132","author":"Waarts","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_19","unstructured":"(2024, April 06). Safety of GM-CT-01 with and without 5-Fluorouracil in Patients with Solid Tumors, Identifier NCT00054977, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/study\/NCT00054977."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"981","DOI":"10.7150\/ijbs.79852","article-title":"Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity","volume":"19","author":"Zheng","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Funkhouser, A.T., Strigenz, A.M., Blair, B.B., Miller, A.P., Shealy, J.C., Ewing, J.A., Martin, J.C., Funk, C.R., Edenfield, W.J., and Blenda, A.V. (2022). KIT mutations correlate with higher galectin levels and brain metastasis in breast and non-small cell lung cancer. Cancers, 14.","DOI":"10.3390\/cancers14112781"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Orrantia-Borunda, E., Anchondo-Nu\u00f1ez, P., Acu\u00f1a-Aguilar, L.E., G\u00f3mez-Valles, F.O., and Ram\u00edrez-Valdespino, C.A. (2022). Subtypes of Breast Cancer. Breast Cancer, Exon Publications.","DOI":"10.36255\/exon-publications-breast-cancer-subtypes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4137\/CPath.S31563","article-title":"Diversity of breast carcinoma: Histological subtypes and clinical relevance","volume":"8","author":"Makki","year":"2015","journal-title":"Clin. Med. Insights Pathol."},{"key":"ref_24","unstructured":"Jones, C. (2024, April 06). Ductal Carcinoma In Situ: The Weight of the Word \u201cCancer\u201d. Available online: https:\/\/www.aacr.org\/blog\/2022\/10\/12\/ductal-carcinoma-in-situ-the-weight-of-the-word-cancer\/."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Blair, B.B., Funkhouser, A.T., Goodwin, J.L., Strigenz, A.M., Chaballout, B.H., Martin, J.C., Arthur, C.M., Funk, C.R., Edenfield, W.J., and Blenda, A.V. (2021). Increased Circulating Levels of Galectin Proteins in Patients with Breast, Colon, and Lung Cancer. Cancers, 13.","DOI":"10.3390\/cancers13194819"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, C.H., Chang, Y.C., Hsiao, M., and Liang, S.M. (2019). FOXD1 and Gal-3 form a positive regulatory loop to regulate lung cancer aggressiveness. Cancers, 11.","DOI":"10.3390\/cancers11121897"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1128\/MCB.00959-05","article-title":"Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis","volume":"26","author":"Cecchinelli","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lavra, L., Rinaldo, C., Ulivieri, A., Luciani, E., Fidanza, P., Giacomelli, L., Bellotti, C., Ricci, A., Trovato, M., and Soddu, S. (2011). The loss of the p53 activator HIPK2 is responsible for galectin-3 overexpression in well differentiated thyroid carcinomas. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020665"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","author":"Koboldt","year":"2012","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"252","DOI":"10.5306\/wjco.v6.i6.252","article-title":"Biomarkers in triple negative breast cancer: A review","volume":"6","author":"Yadav","year":"2015","journal-title":"World J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.2353\/ajpath.2010.090876","article-title":"Overexpression of Galectin-7, A Myoepithelial Cell Marker, Enhances Spontaneous Metastasis of Breast Cancer Cells","volume":"176","author":"Demers","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Campion, C.G., Labrie, M., Lavoie, G., and St-Pierre, Y. (2013). Expression of Galectin-7 Is Induced in Breast Cancer Cells by Mutant p53. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072468"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13987","DOI":"10.1111\/eci.13987","article-title":"Multifaceted role of galectin-4 in cancer: A systematic review","volume":"53","author":"Kaur","year":"2023","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_34","first-page":"10233","article-title":"Overexpression of galectin-4 promotes cell growth of hepatocellular carcinoma cells in vitro and in vivo","volume":"10","author":"Chen","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/818\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:01:39Z","timestamp":1760108499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/6\/818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["genes15060818"],"URL":"https:\/\/doi.org\/10.3390\/genes15060818","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]}}}