Skip to main content
SpringerLink
Log in

Effects of PIM3 in prognosis of colon cancer

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

PIM kinase is called proto-oncogene, but there are less research on PIM family in colon cancer. This study was designed to explore the prognosis of PIM3 in colon cancer.

Methods

In this study, we downloaded RNA-seq and clinical information of colon cancer from the Gene Expression Omnibus (GEO) database. Kaplan–Meier method was used for analyzing the impact of PIM3 on the survival of patients with colon cancer. Single-factor and multi-factor cox regression analysis were used for verifying the prognostic value of PIM3. Spearman correlation analysis was used for screening PIM3 related genes. Functional enrichment analysis was used for analyzing the biological functions and pathways in which PIM3 related genes may be involved. STRING online tools were used for building a co-expression network. Cytoscape was used for co-expression network visualization.

Results

Compared with the low expression group, the patients in the PIM3 high expression group lived longer time. Single-factor and multi-factor cox regression analysis indicated that PIM3 was an independent prognostic factor for colon cancer. Sixty-two PIM3 related genes were screened, and GO and KEGG enrichment analyses suggested that PIM3 related genes might be involved in the MAPK and WNT pathways. The co-expression network showed a strong correlation between PIM3 and MLKL, MYL5, PPP3R1 and other genes.

Conclusions

PIM3 is an independent prognostic factor of colon cancer and may be a target for the diagnosis and treatment of colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941–53.

    Article  CAS  Google Scholar 

  2. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70:145–64.

    Article  Google Scholar 

  3. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394:1467–80.

    Article  Google Scholar 

  4. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111–21.

    Article  CAS  Google Scholar 

  5. Holder SL, Abdulkadir SA. PIM1 kinase as a target in prostate cancer: roles in tumorigenesis, castration resistance, and docetaxel resistance. Curr Cancer Drug Targets. 2014;14:105–14.

    Article  CAS  Google Scholar 

  6. Xu J, Zhang T, Wang T, You L, Zhao Y. PIM kinases: an overview in tumors and recent advances in pancreatic cancer. Future Oncol. 2014;10:865–76.

    Article  CAS  Google Scholar 

  7. Chiang WF, Yen CY, Lin CN, Liaw GA, Chiu CT, Hsia YJ, Liu SY. Up-regulation of a serine-threonine kinase proto-oncogene Pim-1 in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2006;35:740–5.

    Article  Google Scholar 

  8. Yan B, Yau EX, Samanta S, et al. Clinical and therapeutic relevance of PIM1 kinase in gastric cancer. Gastric Cancer. 2012;15:188–97.

    Article  CAS  Google Scholar 

  9. Kuo HP, Ezell SA, Hsieh S, et al. The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma. Am J Cancer Res. 2016;6:2489–501.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Jöhrer K, Obkircher M, Neureiter D, et al. Antimyeloma activity of the sesquiterpene lactone cnicin: impact on Pim-2 kinase as a novel therapeutic target. J Mol Med (Berl). 2012;90:681–93.

    Article  Google Scholar 

  11. Keane NA, Reidy M, Natoni A, Raab MS, O’Dwyer M. Targeting the Pim kinases in multiple myeloma. Blood Cancer J. 2015;5:e325.

    Article  CAS  Google Scholar 

  12. Blanco-Aparicio C, Carnero A. Pim kinases in cancer: diagnostic, prognostic and treatment opportunities. Biochem Pharmacol. 2013;85:629–43.

    Article  CAS  Google Scholar 

  13. Luo H, Sun R, Zheng Y, Huang J, Wang F, Long D, Wu Y. PIM3 promotes the proliferation and migration of acute myeloid leukemia cells. Onco Targets Ther. 2020;13:6897–905.

    Article  CAS  Google Scholar 

  14. Wang G, Liu G, Ye Y, Fu Y, Zhang X. Bufothionine exerts anti-cancer activities in gastric cancer through Pim3. Life Sci. 2019;232:116615.

    Article  CAS  Google Scholar 

  15. Qi Q, Pan Y, Han S, Liao H, Jiang Y, Shen J, Zhong L, Wang X, Chen J. PIM3 functions as oncogenic factor and promotes the tumor growth and metastasis in colorectal cancer. Anat Rec (Hoboken). 2019;302:1552–60.

    Article  CAS  Google Scholar 

  16. Zhou Z, Zhang R, Wang R, Zhang Y, Xu L, Chen J, Zhang J, Huang Z, Chen M, Pan Z. Expression of Pim-3 in colorectal cancer and its relationship with prognosis. Tumour Biol. 2016;37:9151–6.

    Article  CAS  Google Scholar 

  17. Allen WL, Dunne PD, McDade S, et al. Transcriptional subtyping and CD8 immunohistochemistry identifies poor prognosis stage II/III colorectal cancer patients who benefit from adjuvant chemotherapy. JCO Precis Oncol. 2018. https://doi.org/10.1200/PO.17.00241.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kopetz S. New therapies and insights into the changing landscape of colorectal cancer. Nat Rev Gastroenterol Hepatol. 2019;16:79–80.

    Article  CAS  Google Scholar 

  19. Barresi V, Cinnirella G, Valenti G, Spampinato G, Musso N, Castorina S, Condorelli DF. Gene expression profiles in genome instability-based classes of colorectal cancer. BMC Cancer. 2018;18:1265.

    Article  CAS  Google Scholar 

  20. Roerink SF, Sasaki N, Lee-Six H, et al. Intra-tumour diversification in colorectal cancer at the single-cell level. Nature. 2018;556:457–62.

    Article  CAS  Google Scholar 

  21. Mukaida N, Wang YY, Li YY. Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer Sci. 2011;102:1437–42.

    Article  CAS  Google Scholar 

  22. Li YY, Mukaida N. Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression. World J Gastroenterol. 2014;20:9392–404.

    PubMed  PubMed Central  Google Scholar 

  23. Brasó-Maristany F, Filosto S, Catchpole S, et al. PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat Med. 2016;22:1303–13.

    Article  Google Scholar 

  24. Cao T, Jiang N, Liao H, Shuai X, Su J, Zheng Q. The FLT3-ITD mutation and the expression of its downstream signaling intermediates STAT5 and Pim-1 are positively correlated with CXCR4 expression in patients with acute myeloid leukemia. Sci Rep. 2019;9:12209.

    Article  Google Scholar 

  25. Mikkers H, Allen J, Knipscheer P, Romeijn L, Hart A, Vink E, Berns A. High-throughput retroviral tagging to identify components of specific signaling pathways in cancer. Nat Genet. 2002;32:153–9.

    Article  CAS  Google Scholar 

  26. Kitur K, Wachtel S, Brown A, Wickersham M, Paulino F, Penaloza HF, et al. Necroptosis promotes staphylococcus aureus clearance by inhibiting excessive inflammatory signaling. Cell Rep. 2016;16:2219–30.

    Article  CAS  Google Scholar 

  27. Hu B, Shi D, Lv X, Chen S, Huang Q, Xie M, Shao Z. Prognostic and clinicopathological significance of MLKL expression in cancer patients: a meta-analysis. BMC Cancer. 2018;18:736.

    Article  Google Scholar 

  28. Zhang L, Huang ST, Feng YL, et al. The bidirectional regulation between MYL5 and HIF-1alpha promotes cervical carcinoma metastasis. Theranostics. 2017;7:3768–80.

    Article  CAS  Google Scholar 

  29. Wen L, Javed TA, Dobbs AK, et al. The protective effects of calcineurin on pancreatitis in mice depend on the cellular source. Gastroenterology. 2020;159(1036–1050):e1038.

    Google Scholar 

Download references

Funding

Intra-Hospital Fund of the First Hospital of Lanzho University (LDYYYN2019-52); 2020 Gansu Province Health Industry Research Project (GSWSKY2020-12).

Author information

Authors and Affiliations

  1. Department of Geriatrics (II), The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China

    Y. Zhou, S. X. Liu, J. Wang & X. Yan

  2. Department of Gastroenterology, The First Hospital of Lanzhou University, No.1 Donggangxi Road, Chengguan District, Lanzhou, 730000, People’s Republic of China

    Y. N. Zhou & R. Ji

Authors
  1. Y. Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. N. Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. X. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X. Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YuZ and YoZ conceived and designed the study, and drafted the manuscript. YuZ, YoZ, SL, JW, RJ and XY collected, analyzed and interpreted the experimental data. YoZ and SL revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Y. N. Zhou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethical Committee of The First Hospital of Lanzhou University and conducted in accordance with the ethical standards.

Informed consent

Yes.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, Y., Zhou, Y.N., Liu, S.X. et al. Effects of PIM3 in prognosis of colon cancer. Clin Transl Oncol 23, 2163–2170 (2021). https://doi.org/10.1007/s12094-021-02624-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-021-02624-7

Keywords

Search

Navigation