Normal values of IGF1 and IGFBP3. Kučera R., Vrzalová J., Fuchsová R., Topolčan O., Tichopád A.



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Transcription:

Normal values of IGF1 and IGFBP3 Kučera R., Vrzalová J., Fuchsová R., Topolčan O., Tichopád A.

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

IGF system IGFs IGF1, IGF2 IGFBPs IGFBP1...IGFBP6 Receptors for IGFs IGF1R, IGF2R, IR, hybrid receptor IR/IGF1R Signal pathway of IGFs PI3K/PKB, MAP kinases

Function of IGF1 and IGFBP3 Physiological function of IGF1 is absolutely essential for a healthy growth and development of the organism. Regulation of growth, metabolism, survival and differentiation of the cells in postnatal development. IGFBP3 is a most carrier protein of IGF1 and IGF2 in the blood Place of the synthesis of both analytes: liver Indication in routine practice: growth disorders Our topic: IGF1 and cancer

IGF1 Growth factor Molecular weight (Da) Amino acids number IGF1 7 464 70 Physiologic Function Regulation of growth, metabolism, cell survival and differentiation in postnatal development Half-life of free IGF1: <10min Half-life of IGF1/IGFBP3 complex: cca 12h

IGFBP3 Binding protein molecular weight (kda) IGFBP3 53 Binding affinity IGF1, IGF2 Occurrence serum Half-life of IGFBP3: 30min Half-life of IGF1(2)/IGFBP3 complex: cca 12h

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

Why normal values part 1 Group of patients with cancer must be compared with a group of healthy persons IGF1 levels decline with age IGFBP3 levels decline with age We investigate cancer across the spectrum of the adult population (melanoma, prostate, colorectal, ovarian, breast ca)

Why normal values part 2 Serum IGF1 values are affected by various diseases Increased in diabetes and other disorders of the utilization of insulin and glucose metabolism IGF1 determination in cancer is a new indication Increased and decreased levels occur in tumors Increase and decrease is sometimes not very significant

Why normal values part 3 For obtaining correct results, it is necessary to compare the values measured in tumors with normal values of investigated population Small deviation of the investigated population from normal values may cause a wrong conclusion sufficient number of persons in each age group

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

Group of the persons blood donors euthyroid patients, without treatment - patients from Faculty Hospital Pilsen - we excluded patients with diabetes, high blood glucose, high insulin levels, patients after surgery, patients polymorbid and a large number of medications

IGF1 Group Age range (years) Number of persons (N) Number of men (N) Number of women (N) 21 30 103 51 52 31 40 116 60 56 41 50 129 67 62 51 60 162 89 73 61 70 112 63 49 71 and more 45 22 23 Total 667 352 315

IGFBP3 Group Age range (years) Number of persons (N) Number of men (N) Number of women (N) 21 30 100 50 50 31 40 104 52 52 41 50 97 48 49 51 60 101 49 52 Total 452 236 217

Analytical and statistical methods IGF1 IRMA, Beckman Coulter, Immunotech, Marseille IGFBP3 IRMA, Beckman Coulter, Immunotech, Prague The SAS 9.2 (Statistical Analysis Software release 9.2) was used for all statistical analysis.

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

Normal values of IGF1 Age range (years) Number of persons (N) Median (ng/ml) Min Max (ng/ml) 20 30 103 207.6 45.3-416.0 31 40 116 182.4 71.0 341.5 41 50 129 153.0 36.0 299.5 51 60 162 148.5 27.0 339.3 61 70 112 144.2 15.0 264.6 71 and more 45 91.9 11.2 225.5

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

Normal values of IGFBP3 Age range (years) Number of persons (N) Median (ng/ml) Min Max (ng/ml) 20 30 100 2966 1888 4621 31 40 104 2812 1238 4149 41 50 97 2743 1711 4051 51 60 101 2797 1816 4125

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

IGF1 / IGFBP3 ratio Many patients have the same level of IGF1 at very different levels of IGFBP3 and conversely Some authors evaluate the high levels of IGFBP3 as a protective factor and a positive prognostic factor with regard to tumor growth IGF1/IGFBP3 ratio gives a new view on risk and prognosis of cancer

Normal values of IGF1 / IGFBP3 ratio Age range (years) Number of persons (N) Median (ng/ml) Min Max (ng/ml) 20 30 100 0.0694 0.0160 0.1442 31 40 104 0.0654 0.0267 0.1472 41 50 97 0.0550 0.0160 0.1070 51 60 101 0.0546 0.0187 0.1050

Agenda of the presentation IGF1 and IGFBP3 basic characteristic Why normal values Groups of the persons and methods Normal values of IGF1 Normal values of IGFBP3 IGF1/IGFBP3 ratio Conclusion

Conclusion For obtaining correct results, it is necessary to compare the values measured in tumors with normal values of investigated population In our experience: 100 persons in each age group is a minimum number Ideal number: 200 300 persons IGF1/IGFBP3 ratio is a new parameter in evaluation of risk and prognosis of cancer Our work will continue - adding persons into each age group up to number of 200 (300) - adding persons into age group up to 80 years