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Clinicogenomic characterization of prostate cancer liver metastases

Prostate Cancer and Prostatic Diseases volume 25, pages 366–369 (2022)Cite this article

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Abstract

Background

The site of prostate cancer metastasis is an important predictor of oncologic outcomes, however, the clinicogenomic characteristics associated with the site are not well-defined. Herein, we characterize the genomic alterations associated with the metastatic site of prostate cancer.

Methods

We analyzed clinical and genomic data from prostate cancer patients with metastatic disease and known metastatic sites from publicly available targeted sequencing data.

Results

Prostate cancer metastasis to the liver versus other sites of metastasis conferred a high hazard for death in patients with metastatic prostate cancer (HR: 3.96, 95% CI: 2.4–6.5, p < 0.0001). Genomic analysis of metastatic tissues of prostate cancer-specific genes demonstrated that liver metastases were more enriched with MYC amplification (29.5% vs. 9.8%, FDR = 0.001), PTEN deletion (42% vs. 20.8%, FDR = 0.005), and PIK3CB amplification (8.2% vs. 0.9, FDR = 0.005) compared to other sites. No point mutations were significantly associated with liver metastasis compared to other metastatic sites.

Conclusion

Liver metastases in prostate cancer are associated with poor survival and aggressive genomic features, including MYC-amplification, PTEN-deletion, and PIK3CB-amplification. These findings could have prognostic, treatment, and trial implications.

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Fig. 1: Clinicogenomic characterization of prostate cancer liver metastases.

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References

  1. Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.

    Article  CAS  Google Scholar 

  2. Pond GR, Sonpavde G, De Wit R, Eisenberger MA, Tannock IF, Armstrong AJ. The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;65:3–6.

    Article  Google Scholar 

  3. Zhao F, Wang J, Chen M, Chen D, Ye S, Li X, et al. Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population-based study of 16,643 patients. Clin Transl Med. 2019;8:30.

    Article  Google Scholar 

  4. Singh A, Cheedella NKS, Shakil SA, Gulmi F, Kim DS, Wang JC. Liver metastases in prostate carcinoma represent a relatively aggressive subtype refractory to hormonal therapy and short-duration response to docetaxel monotherapy. Can J Addict Med. 2015;6:265–9.

    Google Scholar 

  5. Pouessel D, Gallet B, Bibeau F, Avancès C, Iborra F, Sénesse P, et al. Liver metastases in prostate carcinoma: Clinical characteristics and outcome. BJU Int. 2007;99:807–11.

    Article  CAS  Google Scholar 

  6. Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23:703–13.

    Article  CAS  Google Scholar 

  7. Nguyen B, Mota JM, Nandakumar S, Stopsack KH, Weg E, Rathkopf D, et al. Pan-cancer Analysis of CDK12 alterations identifies a subset of prostate cancers with distinct genomic and clinical characteristics. Eur Urol. 2020. https://doi.org/10.1016/j.eururo.2020.03.024.

  8. Annala M, Vandekerkhove G, Khalaf D, Taavitsainen S, Beja K, Warner EW, et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov. 2018;8:444–57.

    Article  CAS  Google Scholar 

  9. Koh CM, Iwata T, Zheng Q, Bethel C, Yegnasubramanian S, De Marzo AM. Myc enforces overexpression of EZH2 in early prostatic neoplasia via transcriptional and post-transcriptional mechanisms. Oncotarget. 2011;2:669–83.

    Article  Google Scholar 

  10. Labbé DP, Sweeney CJ, Brown M, Galbo P, Rosario S, Wadosky KM, et al. TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup. Clin Cancer Res. 2017;23:7072–83.

    Article  Google Scholar 

  11. Kim KH, Roberts CWM. Targeting EZH2 in cancer. Nat Med. 2016;22:128–34.

    Article  CAS  Google Scholar 

  12. LoRusso PM. Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J Clin Oncol. 2016;34:3803–15.

    Article  Google Scholar 

Download references

Funding

Dr. Mahal is funded by the Prostate Cancer Foundation, American Society for Radiation Oncology, Department of Defense, and the Sylvester Comprehensive Cancer Center.

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Author notes

  1. These authors contributed equally: Mohammed Alshalalfa, Crystal Seldon.

  2. These authors jointly supervised this work: Matthew C. Abramowitz, Brandon A. Mahal.

Authors and Affiliations

  1. Cancer Control Program, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA

    Mohammed Alshalalfa, Crystal Seldon, Ruben Carmona, Sanoj Punnen, Janaki Sharma, Alan Dal Pra, Alan Pollack, Matthew C. Abramowitz & Brandon A. Mahal

  2. Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA

    Idalid Franco

  3. Department of Urology, University of Michigan, Ann Arbor, MI, USA

    Randy Vince

  4. Baylor College of Medicine, Houston, TX, USA

    Salma Kaochar

  5. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA

    Robert Dess & Daniel E. Spratt

  6. Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Amar Kishan

Authors
  1. Mohammed Alshalalfa
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  14. Matthew C. Abramowitz
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  15. Brandon A. Mahal
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Contributions

MA, CS, IF, and BM conducted the analysis, drafted the paper, and contributed to revisions. MA and AP contributed to data acquisition and critical revision for important content. RV, RC, SP, SK, RD, AK, DS, JS, and ADP contributed to the conception of the study, data acquisition, and critical revision for important content. MA, CS, and BM have responsibility for the final approval of the version to be published.

Corresponding author

Correspondence to Brandon A. Mahal.

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Competing interests

Dr. Mahal is funded by the Prostate Cancer Foundation-American Society for Radiation Oncology Award to End Prostate Cancer (grant support). Dr. Franco is funded by an NIH NCI Center to Reduce Cancer Health Disparities Diversity Supplement, and ACRO Luther Brady Educational Award (grant support). Dr. Spratt has received personal fees: Janssen, Blue Earth, Boston Scientific, AstraZeneca, and funding from Janssen. The remaining authors declare that they have no conflicts of interest.

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Alshalalfa, M., Seldon, C., Franco, I. et al. Clinicogenomic characterization of prostate cancer liver metastases. Prostate Cancer Prostatic Dis 25, 366–369 (2022). https://doi.org/10.1038/s41391-021-00486-2

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  • DOI: https://doi.org/10.1038/s41391-021-00486-2

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