Multilevel Heterogeneity of Colorectal Cancer Liver Metastasis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jan 11

PMID 38201487

Authors

Hao Chen

Chongya Zhai

Xian Xu

Haidong Wang

Weidong Han

Jiaying Shen

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer liver metastasis (CRLM) is a highly heterogeneous disease. Therapies that target both primary foci and liver metastasis are severely lacking. Therefore, understanding the features of metastatic tumor cells in the liver is valuable for the overall control of CRLM patients. In this review, we summarize the heterogeneity exhibited in CRLM from five aspects (gene, transcriptome, protein, metabolism, and immunity). In addition to genetic heterogeneity, the other four aspects exhibit significant heterogeneity. Compared to primary CRC, the dysregulation of epithelial-mesenchymal transition (EMT)-related proteins, the enhanced metabolic activity, and the increased infiltration of immunosuppressive cells are detected in CRLM. Preclinical evidence shows that targeting the EMT process or enhancing cellular metabolism may represent a novel approach to increasing the therapeutic efficacy of CRLM.

References

Vakiani E, Janakiraman M, Shen R, Sinha R, Zeng Z, Shia J . Comparative genomic analysis of primary versus metastatic colorectal carcinomas. J Clin Oncol. 2012; 30(24):2956-62. PMC: 3417049. DOI: 10.1200/JCO.2011.38.2994. View

Thakral S, Ghoshal K . miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Ther. 2014; 15(2):142-50. PMC: 4439190. DOI: 10.2174/1566523214666141224095610. View

Zhang C, Zhou X, Geng X, Zhang Y, Wang J, Wang Y . Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma. Cell Death Dis. 2021; 12(5):443. PMC: 8097074. DOI: 10.1038/s41419-021-03714-8. View

Zhang K, Zhu W, Wang S, Gao C, Pan J, Du Z . Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer. Theranostics. 2021; 11(13):6560-6572. PMC: 8120208. DOI: 10.7150/thno.55609. View

Tsai W, Hsu P, Lai T, Chau G, Lin C, Chen C . MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009; 49(5):1571-82. DOI: 10.1002/hep.22806. View

Miranda E, Bianchi P, Destro A, Morenghi E, Malesci A, Santoro A . Genetic and epigenetic alterations in primary colorectal cancers and related lymph node and liver metastases. Cancer. 2012; 119(2):266-76. DOI: 10.1002/cncr.27722. View

Yang M, Guo Y, Liu X, Liu N . HMGA1 Promotes Hepatic Metastasis of Colorectal Cancer by Inducing Expression of Glucose Transporter 3 (GLUT3). Med Sci Monit. 2020; 26:e924975. PMC: 7532698. DOI: 10.12659/MSM.924975. View

Qi J, Sun H, Zhang Y, Wang Z, Xun Z, Li Z . Single-cell and spatial analysis reveal interaction of FAP fibroblasts and SPP1 macrophages in colorectal cancer. Nat Commun. 2022; 13(1):1742. PMC: 8976074. DOI: 10.1038/s41467-022-29366-6. View

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

10.

Hur K, Toiyama Y, Schetter A, Okugawa Y, Harris C, Boland C . Identification of a metastasis-specific MicroRNA signature in human colorectal cancer. J Natl Cancer Inst. 2015; 107(3). PMC: 4334826. DOI: 10.1093/jnci/dju492. View

11.

Santos C, Azuara D, Vieitez J, Paez D, Falco E, Elez E . Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial. Ann Oncol. 2019; 30(5):796-803. DOI: 10.1093/annonc/mdz082. View

12.

Brannon A, Vakiani E, Sylvester B, Scott S, McDermott G, Shah R . Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol. 2014; 15(8):454. PMC: 4189196. DOI: 10.1186/s13059-014-0454-7. View

13.

Liu Y, Guo F, Zhu X, Guo W, Fu T, Wang W . Death Domain-Associated Protein Promotes Colon Cancer Metastasis through Direct Interaction with ZEB1. J Cancer. 2020; 11(3):750-758. PMC: 6959037. DOI: 10.7150/jca.34233. View

14.

Li Z, Huang C, Bao C, Chen L, Lin M, Wang X . Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015; 22(3):256-64. DOI: 10.1038/nsmb.2959. View

15.

Serrano M, Hannon G, Beach D . A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993; 366(6456):704-7. DOI: 10.1038/366704a0. View

16.

Geissmann F, Gordon S, Hume D, Mowat A, Randolph G . Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol. 2010; 10(6):453-60. PMC: 3032581. DOI: 10.1038/nri2784. View

17.

Vitale I, Shema E, Loi S, Galluzzi L . Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat Med. 2021; 27(2):212-224. DOI: 10.1038/s41591-021-01233-9. View

18.

Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P . Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26(35):5705-12. DOI: 10.1200/JCO.2008.18.0786. View

19.

Li Y, Zhao Z, Xu C, Zhou Z, Zhu Z, You T . HMGA2 induces transcription factor Slug expression to promote epithelial-to-mesenchymal transition and contributes to colon cancer progression. Cancer Lett. 2014; 355(1):130-40. DOI: 10.1016/j.canlet.2014.09.007. View

20.

Teng S, Li Y, Yang M, Qi R, Huang Y, Wang Q . Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer. Cell Res. 2019; 30(1):34-49. PMC: 6951341. DOI: 10.1038/s41422-019-0259-z. View