Investigating the WNT and TGF-beta pathways alterations and tumor mutant burden in young-onset colorectal cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
received:
16
03
2024
accepted:
30
07
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
epublish
Résumé
Colorectal cancer (CRC) is the third most common cancer in the United States. Recent epidemiological evidence demonstrates an increasing incidence of young-onset CRC cases, defined as CRC cases in individuals 50 years old or younger. Studies have established that alterations in both the WNT and TGF-Beta signaling pathways have contributed to CRC development. While this is well understood, the comprehensive analysis of WNT and TGF-Beta pathway alterations in young-onset CRC cases has yet to be investigated. Here, we conducted a comprehensive bioinformatics analysis of mutations associated with each of the WNT and TGF-Beta signaling pathways according to age (≤ 50 years old versus > 50 years old) utilizing published genomic data from the cBioPortal. Chi-square results demonstrated no significant difference in WNT alterations between young-onset CRC and those > 50 years old. However, across all age groups, WNT alterations were frequently found in rectal cancers. We also found that WNT alterations were associated with better outcomes. The mutations associated with TGF-beta were observed at a higher rate in older CRC patients when compared to those ≤ 50 years old. Additionally, these mutations were found more frequently in colon primaries.
Identifiants
pubmed: 39095553
doi: 10.1038/s41598-024-68938-y
pii: 10.1038/s41598-024-68938-y
doi:
Substances chimiques
Transforming Growth Factor beta
0
Wnt Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17884Informations de copyright
© 2024. The Author(s).
Références
Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 68, 394–424 (2018).
doi: 10.3322/caac.21492
pubmed: 30207593
Sinicrope, Frank. Increasing Incidence of Early-Onset Colorectal Cancer; NEJM
Bhandari, A., Woodhouse, M. & Gupta, S. Colorectal cancer is a leading cause of cancer incidence and mortality among adults younger than 50 years in the USA: A SEER-based analysis with comparison to other young-onset cancers. J. Investig. Med. 65, 311–315 (2017).
doi: 10.1136/jim-2016-000229
pubmed: 27864324
Siegel, R. L. et al. Colorectal cancer statistics, 2020. CA. Cancer J. Clin. 70, 145–164 (2020).
doi: 10.3322/caac.21601
pubmed: 32133645
Mauri, G. et al. Early-onset colorectal cancer in young individuals. Mol. Oncol. 13(2), 109–131. https://doi.org/10.1002/1878-0261.12417 (2019).
doi: 10.1002/1878-0261.12417
pubmed: 30520562
Done, J. Z. & Fang, S. H. Young-onset colorectal cancer: A review. World J. Gastrointest. Oncol. 13(8), 856–866. https://doi.org/10.4251/wjgo.v13.i8.856 (2021).
doi: 10.4251/wjgo.v13.i8.856
pubmed: 34457191
pmcid: 8371519
Antelo, M. et al. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. PLoS One 7(9), e45357. https://doi.org/10.1371/journal.pone.0045357 (2012).
doi: 10.1371/journal.pone.0045357
pubmed: 23049789
pmcid: 3458035
Bugter, J. M., Fenderico, N. & Maurice, M. M. Mutations and mechanisms of WNT pathway tumour suppressors in cancer. Nat. Rev. Cancer 21(1), 5–21 (2021).
doi: 10.1038/s41568-020-00307-z
pubmed: 33097916
Xu, Y. & Pasche, B. TGF-β signaling alterations and susceptibility to colorectal cancer. Human Molecular Genetics 16(R1), R14–R20 (2007).
doi: 10.1093/hmg/ddl486
pubmed: 17613544
Chatila, W. K. et al. Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers. Nat. Commun. 14(1), 110. https://doi.org/10.1038/s41467-022-35592-9 (2023).
doi: 10.1038/s41467-022-35592-9
pubmed: 36611031
pmcid: 9825391
Cercek, A. et al. A comprehensive comparison of early-onset and average-onset colorectal cancers. J. Natl. Cancer Inst. 113(12), 1683–1692. https://doi.org/10.1093/jnci/djab124 (2021).
doi: 10.1093/jnci/djab124
pubmed: 34405229
pmcid: 8634406
Chatila, W. K. et al. Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer. Nat. Med. 28(8), 1646–1655. https://doi.org/10.1038/s41591-022-01930-z (2022).
doi: 10.1038/s41591-022-01930-z
pubmed: 35970919
pmcid: 9801308
Giannakis, M. et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep. 15(4), 857–865. https://doi.org/10.1016/j.celrep.2016.03.075 (2016).
doi: 10.1016/j.celrep.2016.03.075
pubmed: 27149842
pmcid: 4850357
Seshagiri, S. et al. Recurrent R-spondin fusions in colon cancer. Nature. 488(7413), 660–664. https://doi.org/10.1038/nature11282 (2012).
doi: 10.1038/nature11282
pubmed: 22895193
pmcid: 3690621
Brannon, A. R. et al. Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol. 15(8), 454. https://doi.org/10.1186/s13059-014-0454-7 (2014).
doi: 10.1186/s13059-014-0454-7
pubmed: 25164765
pmcid: 4189196
Yaeger, R. et al. Molecular characterization of acquired resistance to KRASG12C-EGFR inhibition in colorectal cancer. Cancer Discov. 13(1), 41–55. https://doi.org/10.1158/2159-8290.Cd-22-0405 (2023).
doi: 10.1158/2159-8290.Cd-22-0405
pubmed: 36355783
Mondaca, S. et al. Specific mutations in APC, but not alterations in DNA damage response, associate with outcomes of patients with metastatic colorectal cancer. Gastroenterology 159(5), 1975-1978.e4. https://doi.org/10.1053/j.gastro.2020.07.041 (2020).
doi: 10.1053/j.gastro.2020.07.041
pubmed: 32730818
Gularte-Mérida, R. et al. Same-cell Co-occurrence of RAS hotspot and BRAF V600E mutations in treatment-Naive colorectal cancer. JCO Precis Oncol. 6, e2100365. https://doi.org/10.1200/po.21.00365 (2022).
doi: 10.1200/po.21.00365
pubmed: 35235413
pmcid: 8906458
Alatise, O. I. et al. Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights. Nat. Commun. 12(1), 6821. https://doi.org/10.1038/s41467-021-27106-w (2021).
doi: 10.1038/s41467-021-27106-w
pubmed: 34819518
pmcid: 8613248
Yaeger, R. et al. Clinical sequencing defines the genomic landscape of metastatic colorectal cancer. Cancer Cell. 33(1), 125-136.e3. https://doi.org/10.1016/j.ccell.2017.12.004 (2018).
doi: 10.1016/j.ccell.2017.12.004
pubmed: 29316426
pmcid: 5765991
Guda, K. et al. Novel recurrently mutated genes in African American colon cancers. Proc. Natl. Acad. Sci. USA. 112(4), 1149–1154. https://doi.org/10.1073/pnas.1417064112 (2015).
doi: 10.1073/pnas.1417064112
pubmed: 25583493
pmcid: 4313860
Vasaikar, S. et al. Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities. Cell 177(4), 1035-1049.e19. https://doi.org/10.1016/j.cell.2019.03.030 (2019).
doi: 10.1016/j.cell.2019.03.030
pubmed: 31031003
pmcid: 6768830
Roelands, J. et al. An integrated tumor, immune and microbiome atlas of colon cancer. Nat. Med. 29(5), 1273–1286. https://doi.org/10.1038/s41591-023-02324-5 (2023).
doi: 10.1038/s41591-023-02324-5
pubmed: 37202560
pmcid: 10202816
Cerami, E. et al. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2(5), 401–404. https://doi.org/10.1158/2159-8290.Cd-12-0095 (2012).
doi: 10.1158/2159-8290.Cd-12-0095
pubmed: 22588877
Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics. CA Cancer J. Clin. 73(1), 17–48 (2023).
doi: 10.3322/caac.21763
pubmed: 36633525
Ahnen, D. J. et al. The increasing incidence of young-onset colorectal cancer: A call to action 216–224 (Elsevier, 2014).
Patel, S. G., Karlitz, J. J., Yen, T., Lieu, C. H. & Boland, C. R. The rising tide of early-onset colorectal cancer: A comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol. Hepatol. 7(3), 262–274 (2022).
doi: 10.1016/S2468-1253(21)00426-X
pubmed: 35090605
Terzić, J., Grivennikov, S., Karin, E. & Karin, M. Inflammation and colon cancer. Gastroenterology 138(6), 2101–2114 (2010).
doi: 10.1053/j.gastro.2010.01.058
pubmed: 20420949
Watson, R., Liu, T.-C. & Ruzinova, M. B. High frequency of KRAS mutation in early onset colorectal adenocarcinoma: Implications for pathogenesis. Human pathol. 56, 163–170 (2016).
doi: 10.1016/j.humpath.2016.06.010
Lieu, C. H. et al. Comprehensive genomic landscapes in early and later onset colorectal cancer. Clin. Cancer Res. 25(19), 5852–5858 (2019).
doi: 10.1158/1078-0432.CCR-19-0899
pubmed: 31243121
pmcid: 6774873
Sahin, I.H., Xiu, J, Khushman, MdM, et al. Association of class II and III BRAF mutations with EGFR blockade therapy response and representation of molecularly distinct subgroups of BRAF mutations in MMR proficient CRC. American Society of Clinical Oncology. (2024).
Jass, J. R. HNPCC and sporadic MSI-H colorectal cancer: A review of the morphological similarities and differences. Familial Cancer. 3, 93–100 (2004).
doi: 10.1023/B:FAME.0000039849.86008.b7
pubmed: 15340259
Segditsas, S. & Tomlinson, I. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 25(57), 7531–7537 (2006).
doi: 10.1038/sj.onc.1210059
pubmed: 17143297
Grant, A. et al. Molecular drivers of tumor progression in microsatellite stable APC mutation-negative colorectal cancers. Sci. Rep. 11(1), 23507 (2021).
doi: 10.1038/s41598-021-02806-x
pubmed: 34873211
pmcid: 8648784
Half, E., Bercovich, D. & Rozen, P. Familial adenomatous polyposis. Orphanet J. Rare Dis. 4(1), 1–23 (2009).
doi: 10.1186/1750-1172-4-22
Guinney, J. et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 21(11), 1350–1356 (2015).
doi: 10.1038/nm.3967
pubmed: 26457759
pmcid: 4636487
Bellam, N. & Pasche, B. TGF-β signaling alterations and colon cancer. Cancer Gen. https://doi.org/10.1007/978-1-4419-6033-7_5 (2010).
doi: 10.1007/978-1-4419-6033-7_5
Markowitz, S. D. & Roberts, A. B. Tumor suppressor activity of the TGF-β pathway in human cancers. Cytokine Growth Factor Rev. 7(1), 93–102 (1996).
doi: 10.1016/1359-6101(96)00001-9
pubmed: 8864357
Li, F., Cao, Y., Townsend, C. M. & Ko, T. C. TGF-β signaling in colon cancer cells. World J. Surg. 29, 306–311 (2005).
doi: 10.1007/s00268-004-7813-6
pubmed: 15711891
Lee, M. S., Menter, D. G. & Kopetz, S. Right versus left colon cancer biology: integrating the consensus molecular subtypes. J. Nat. Comprehensive Cancer Netw. 15(3), 411–419 (2017).
doi: 10.6004/jnccn.2017.0038