Shtabinskaya T.T.

Grodno State Medical University, Belarus

The prognostic significance of the expression of angiogenic markers in low-grade colon cancer in I-II stage of disease

Relatively favorable morphological features of any tumor are low grade and early stage of the disease.However, the survival rate of patients with the same morphological features is different. Purpose: to determine the value of angiogenic markers expression in I-II stages of low-grade CRC for the prognosis of the disease.

Materials and methods: 21 cases of low-grade CRC I-II stage were investigated. The study was performed on paraffin sections using antibodies to VEGFА, CD 105, MMP-2, Erk2, iNOS, TGF-β, NRP1, MMP-9 according to standard procedure [1]. Quantitation of the level of expression was described in the previous article  [2]. Statistical analysis was performed using STATISTICA 10.0 (SNAXAR207F394425FA-Q).

Results: Statistically significant differences in the expression of markers of angiogenesis in patients stage I, depending on the five-year adjusted disease-free survival (AFS) haven’t been identified. In patients with stage II disease were statistically significant differences in the expression of  VEGFA, NRP1, iNOS, and TGF-β. Using ROC-analysis identified the split point for the five-year prediction AFS depending on the level of stromal VEGFA expression (fig.1).

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Figure 1 - ROC curve for the AFS prediction in patients with stage II disease, depending on the level of stromal expression VEGFA

The area under the ROC-curve constructed through the analysis, equal to 0,81 ± 0,13 (the accuracy of the differences with the area under the diagonal = 0.017). The most distant point from the diagonal to the ROC-curve corresponds to the level of expression VEGFA equal to 0.978 (sensitivity - 83.3%, specificity - 87.5%).

The area under the ROC-curve constructed through the analysis of the expression of stromal NRP1, equal to 0,92 ± 0,08 (with the accuracy of the differences below the diagonal area <0.0001) (fig.2). The most distant point from the diagonal to the ROC-curve corresponds to the level of expression of NRP1 equal to 0.747 (sensitivity - 100%, specificity - 75%).

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Figure 2 - ROC curve for the AFS prediction in patients with stage II disease, depending on the level of stromal expression NRP1

The area under the ROC-curve constructed through the analysis of parenchymal TGF-β expression is equal to 0,98 ± 0,03 (the accuracy of the differences with the area under the diagonal <0.0001) (fig.3). The most distant point from the diagonal to the ROC-curve corresponds to the expression of TGF-β equal to 0.682 (sensitivity - 100%, specificity - 85.7%).

The area under the ROC-curve constructed through the analysis of the general expression of iNOS, equal to 0,84 ± 0,11 (the accuracy of the differences with the area under the diagonal = 0.0013) (fig.4). The most distant point from the diagonal to the ROC-curve corresponds to expression of iNOS is 0.69 (sensitivity - 83.3%, specificity - 75%).

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Figure 3 - ROC curve for the AFS prediction in patients with stage II disease, depending on the level of parenchymal expression of TGF-β

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Figure 4 - ROC curve for the AFS prediction in patients with stage II disease, depending on the level of general expression of iNOS

Conclusion: Favorable outcome (survival rate of more than 5 years), low-grade colon cancer in the II stage predict when stromal expression VEGF≤0.978, parenchymal - TGF-β≤0.682, stromal - NRP1> 0.747, general - iNOS≤0.69.

Literature:

1.   Коржевский, Д.Э. Основы гистологической техники / Д.Э. Коржевский, А.В. Гиляров. – Спб.: СпецЛит, 2010. – 95 с.

2.        Штабинская, Т.Т. Прогностическое значение уровня экспрессии фактора роста эндотелия сосудов в колоректальном раке / Т.Т. Штабинская [и др.] // Научно-практический журнал УО «Гродненский государственный медицинский университет». – 2015. - № 3(51). - С. 64-69.