EPMA Journal

, Volume 10, Issue 3, pp 307–316 | Cite as

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

  • Marija MihajlovicEmail author
  • Ana Ninic
  • Miron Sopic
  • Milica Miljkovic
  • Aleksandra Stefanovic
  • Jelena Vekic
  • Vesna Spasojevic-Kalimanovska
  • Dejan Zeljkovic
  • Bratislav Trifunovic
  • Zeljka Stjepanovic
  • Aleksandra Zeljkovic



Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC.


Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin’s concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism.


Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers.


Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin’s secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.


Resistin Adenylate cyclase-associated protein 1 High-density lipoprotein cholesterol Paraoxonase-1 activity Colorectal cancer Predictive preventive personalized medicine 


Authors’ contribution

MM (corresponding author) performed laboratory measurements, statistical analysis, and wrote the first draft of the manuscript. AN, MS, MM, and AS contributed to experimental design and participated in laboratory analyses. DZ, BT, and ZS were involved in protocol development, patient recruitment, and data acquisition. JV and VSK provided intellectual guidance and critically reviewed the manuscript. AZ conceived and designed the study and critically reviewed the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Funding information

This work was supported by a grant from the Ministry of Education, Science and Technological Development, Republic of Serbia (Project No. 175035).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The entire study protocol was designed according to the Helsinki Declaration and approved by the local ethical committee (The Ethics committee of the Military Medical Academy; Ethics Committee reference no. 3000-1).


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Copyright information

© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2019

Authors and Affiliations

  • Marija Mihajlovic
    • 1
    Email author
  • Ana Ninic
    • 1
  • Miron Sopic
    • 1
  • Milica Miljkovic
    • 1
  • Aleksandra Stefanovic
    • 1
  • Jelena Vekic
    • 1
  • Vesna Spasojevic-Kalimanovska
    • 1
  • Dejan Zeljkovic
    • 2
  • Bratislav Trifunovic
    • 2
    • 3
  • Zeljka Stjepanovic
    • 4
  • Aleksandra Zeljkovic
    • 1
  1. 1.Department of Medical Biochemistry, Faculty of PharmacyUniversity of BelgradeBelgradeSerbia
  2. 2.Clinic of General SurgeryMilitary Medical AcademyBelgradeSerbia
  3. 3.Faculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgradeSerbia
  4. 4.Medigroup General HospitalBelgradeSerbia

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