Skip to main content
SpringerLink
Log in

CD38 gene polymorphism rs1130169 contribution to the increased gene expression and risk of colorectal cancer (pilot study)

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Genetic variations in immune signaling genes may have regulatory effect on phenotypic heterogeneity of immune cells and immune functions, hence promoting tumor growth.

Purpose

We compared the frequencies of potentially functional CD38 gene single nucleotide polymorphisms rs1130169 (T > C) in 86 healthy controls and 90 colorectal cancer (CRC) cases to assess their association with cancer risk and CD38 gene expression.

Results

The association between allele C rs1130169 and CRC risk was observed. Allele C was also significantly correlated with an increased CD38 mRNA level and CD38 positive cell percentages in peripheral blood of healthy controls that could be a possible explanation for CRC risk in C allele carriers. In peripheral blood of CRC patients CD38 mRNA and serum soluble CD38 protein levels significantly differed from those in healthy controls. Calculation of the CD38 full-length and with the third exon deletion mRNA ratio in corresponding samples showed that the mRNA isoform ratio was significantly higher in CRC cases than in controls. It suggests that alternative splicing regulates elevation of CD38 full-length mRNA level in peripheral blood of CRC patients. We also have observed higher expression levels of CD38 full-length mRNA in peripheral blood of CRC patients with lymph node metastases compared to patients without metastases.

Conclusion

This study indicated biological significance of rs1130169 variations that can alter differences in CRC risk by regulating CD38 gene expression.

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

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Chang CM, Chia VM, Gunter MJ et al (2013) Innate immunity gene polymorphisms and the risk of colorectal neoplasia. Carcinogenesis 34:2512–2520. https://doi.org/10.1093/carcin/bgt228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cho YA, Lee J, Oh JH, Chang HJ, Sohn DK, Shin A, Kim J (2019) Genetic risk score, combined lifestyle factors and risk of colorectal cancer. Cancer Res Treat: Off J Korean Cancer Assoc 51(3):1033–1040. https://doi.org/10.4143/crt.2018.447

    Article  CAS  Google Scholar 

  3. Hogan KA, Chini CC, Chini EN (2019) The multi-faceted ecto-enzyme CD38: roles in immunomodulation, cancer, aging, and metabolic diseases. Front Immunol 10:1187. https://doi.org/10.3389/fimmu.2019.01187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Takasawa S (2022) CD38–Cyclic ADP-ribose signal system in physiology, biochemistry, and pathophysiology. Int J Mol Sci 23(8):4306. https://doi.org/10.3390/ijms23084306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Higashida H, Yokoyama S, Huang JJ, Liu L, Ma W-J, Akther S, Higashida C, Kikuchi M, Minabe Y, Munesue T (2012) Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38. Neurochem Int 61:828–838. https://doi.org/10.1016/j.neuint.2012.01.030

    Article  CAS  PubMed  Google Scholar 

  6. Shahrabi S, Ghanavat M, Behzad MM, Purrahman D, Saki N (2020) CD markers polymorphisms as prognostic biomarkers in hematological malignancies. Oncol Rev 14(2):99–100. https://doi.org/10.4081/oncol.2020.466

    Article  CAS  Google Scholar 

  7. Jamroziak K, Szemraj Z, Grzybowska-Izydorczyk O et al (2009) CD38 gene polymorphisms contribute to genetic susceptibility to B-cell chronic lymphocytic leukemia: evidence from two case-control studies in polish caucasians. Cancer Epidemiol Biomarkers Prev 18(3):945–953. https://doi.org/10.1158/1055-9965

    Article  CAS  PubMed  Google Scholar 

  8. Hartman WR, Pelleymounter LL, Moon I, Kalari K, Liu M, Wu TY, Escande C, Nin V, Chini EN, Weinshilboum RM (2010) CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model system. Leuk Lymphoma 51:1315–1325. https://doi.org/10.3109/10428194.2010.483299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lebedev M, Egorova NI, Sholkina MN, Vilkov SA, Baryshnikov AJ, Novikov VV (2004) Serum levels of different forms of soluble CD38 antigen in burned patients. Burns 30:552–556. https://doi.org/10.1016/j.burns.2004.01.029

    Article  PubMed  Google Scholar 

  10. Cikos S, Bukovska A, Koppel J (2007) Relative quantification of mRNA: comparison of methods currently used for real-time PCR data analysis. BMC Mol Biol 8:113. https://doi.org/10.1186/1471-2199-8-113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mallone R, Ferrua S, Morra M, Zocchi E, Mehta K, Notarangelo LD, Malavasi F (1998) Characterization of a CD38 like 78 kilodalton soluble protein released from B cell lines derived from patients with X linked agammaglobulinemia. J Clin Invest 101:2821–2830. https://doi.org/10.1172/JCI1068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Perenkov AD, Novikov DV, Sakharnov NA, Aliasova AV, Utkin OV, Alu B, Novikov VV (2012) Heterogeneous expression of CD38 gene in tumor tissue in patients with colorectal cancer. Mol Biol (Mosk) 46:786–791

    Article  CAS  PubMed  Google Scholar 

  13. Ogino S, Nosho K, Irahara N, Shima K, Baba Y, Kirkner GJ, Mino-Kenudson M, Giovannucci EL, Meyerhardt JA, Fuchs CS (2010) Negative lymph node count is associated with survival of colorectal cancer patients, independent of tumoral molecular alterations and lymphocytic reaction. Am J Gastroenterol 105:420–433. https://doi.org/10.1038/ajg.2009.578

    Article  PubMed  Google Scholar 

  14. Bahri R, Bollinger A, Bollinger T, Orinska Z, Bulfone-Paus S (2012) Ectonucleotidase CD38 demarcates regulatory, memory-like CD8 + T cells with IFN-c-mediated suppressor activities. PLoS ONE 7:e45234. https://doi.org/10.1371/journal.pone.0045234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Deaglio S, Robson SC (2011) Ectonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunity. Adv Pharmacol 61:301–332. https://doi.org/10.1016/B978-0-12-385526-8.00010-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Masuda K, Kornberg A, Miller J, Lin S, Suek N, Botella T, Secener KA, Bacarella AM, Cheng L, Ingham M, Rosario V, Al-Mazrou AM, Lee-Kong SA, Kiran RP, Stoeckius M, Smibert P, Del Portillo A, Oberstein PE, Sims PA, Yan KS, Han A (2022) Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer. JCI Insight 7(7):e154646. https://doi.org/10.1172/jci.insight.154646

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all participants and Alexander V. Kalugin for their help in samples collection. Research was supported by the Ministry of education and science of Russian Federation to perform public works in the field of scientific activities: task 2014/134(2575). This work was supported by the Strategic Academic Leadership Program of Kazan Federal University.

Funding

No funding was obtained for this study.

Author information

Authors and Affiliations

  1. I.N. Blokhina Research Institute of Epidemiology and Microbiology, Malaya Yamskaya Str. 71, Nizhny Novgorod, Russia, 603950

    Dmitry V. Novikov & Viktor V. Novikov

  2. Lobachevsky State University of Nizhny Novgorod, Gagarin Str. 23, Nizhny Novgorod, Russia, 603950

    Dmitry V. Novikov, Alexei D. Perenkov, Svetlana V. Shumilova & Viktor V. Novikov

  3. Kazan Federal University, Kremlyovskaya St. 18, Kazan, Russia, 420000

    Nailya I. Kubysheva

Authors
  1. Dmitry V. Novikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexei D. Perenkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Svetlana V. Shumilova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nailya I. Kubysheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Viktor V. Novikov
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ADP, VVN conceived and designed the experiments. DVN, ADP, SVS, NIK made contributions to the data collection and analysis and wrote the manuscript. ADP, DVN prepared Figs. 1 and 2. All authors reviewed the manuscript.

Corresponding author

Correspondence to Nailya I. Kubysheva.

Ethics declarations

Conflict of interest

The authors declare that there is no potential conflict of interest associated with this manuscript.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki and this research was reviewed and approved by the Ethics Committee of the Nizhny Novgorod I.N. Blokhina Research Institute of Epidemiology and Microbiology November 25, 2021, protocol No. 6.

Consent to participate

All subjects gave written informed consent to the use of their blood samples for research purposes.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novikov, D.V., Perenkov, A.D., Shumilova, S.V. et al. CD38 gene polymorphism rs1130169 contribution to the increased gene expression and risk of colorectal cancer (pilot study). Mol Biol Rep 51, 63 (2024). https://doi.org/10.1007/s11033-023-09034-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11033-023-09034-8

Keywords

Search

Navigation