Shtabinskaya T.T., Kendysh E.N., Bodnar M.

Grodno State Medical University, Belarus

TGF-β expression in colorectal adenocarcinoma depending on lymphogenic dissemination

Lymphogenic dissemination is the determining factor of the prognosis of colorectal adenocarcinoma, whose role is not disputed by scientists. When the disease is detected in the early stages (stages I-II), the level of five-year survival is quite high: 93.2% and 72.2%, respectively. However, as the tumor grows and regional lymph nodes become involved in the process, there is a sharp decline in this indicator to 44.3% (stage III) [1].

At present, the role of TGF-β in the processes of malignant transformation and tumor progression is ambiguous. By directly and indirectly activating several signaling pathways, it can be both a tumor promoter and a tumor suppressor [2, 3].

Prokonogenic activity is realized through the epithelial-mesenchymal transition, as well as during the formation of immune suppression.

In the later stages of carcinogenesis, TGF-β, on the contrary, suppresses tumor growth. This is primarily the ability of TGF-β to regulate the cell cycle by inducing the synthesis of inhibitors of cyclin-dependent kinases, which leads to the arrest of the cell cycle in the G1 phase. Due to the activation of telomerase, TGF-β is also capable of inducing apoptosis of epithelial, endothelial, hematopoietic cells.

Purpose: to assess expression of TGF-β in colorectal adenocarcinoma depending on lymphogenic dissemination and its significance for predicting the course of the disease.

Materials and methods: 72 cases of colorectal adenocarcinoma were investigated. The study was performed on paraffin sections using polyclonal antibodies to TGF-β (ab66043) according to standard procedure. Quantitation of the level of expression was described in the previous article [4]. Statistical analysis was performed using STATISTICA 10.0 (SNAXAR207F394425FA-Q).

Results:

In 44 patients (61.1%) of the study group at the time of registration, metastases were found in the regional lymph nodes (pN1b - 29 cases, pN1c - 4, pN2a - 11). During the follow-up from the progression of the disease, 37 patients died (51.4%). The median of the adjusted disease-free survival was 2.5 (1.6-4.2) years.

Positivity levels of TGF- β a were determined in the parenchymal and stromal components of the tumor, as well as the overall level of positivity (Table 1).

Table 1 – Expression of TGF-β depending on lymphogenic dissemination

Expression positivity		Lymphogenic dissemination		p
		рN0	рN1-2
	Parenchymal	0,820 (0,580-0,947)	0,690 (0,380-0,880)	0,053
	Stromal	0,460 (0,171-0,680)	0,269 (0,105-0,577)	0,175

The area of TGF-β expression in the parenchymal component of colorectal adenocarcinoma without lymphogenous metastases is significantly higher than in adenocarcinomas with metastases (p = 0.053).

The construction of a multi-factor model for predicting the 5-year outcome, depending on lymphogenous spread and TGF-β expression, was carried out using Cox regression by a direct step-by-step method. The grouping sign was the outcome of cancer at 5 years from the moment of surgery, as assessed by the adjusted disease-free survival. Authentically, the presence of lymphogenous and haematogenic metastases influenced the five-year survival rate.

 The values of the likelihood function, the statistical criteria of the model for each of the regression steps, the numerical values of the coefficients of independent variables and their characteristics are described in the article [5].

Conclusion: Low expression of TGF-β in colorectal adenocarcinoma indicates lymphogenous dissemination of the tumor, but as an independent prognostic factor it should not be used.

Literature:

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2. Gajdusek, C. M. Вasic fibroblast growth factor and transforming growth factor beta-1: synergistic mediators of angiogenesis in vitro / C. M. Gajdusek, Z. Luo,
M. R. Mayberg // J. Cell Physiol. – 1993. – № 157. – Р. 133-144.

3. Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis / I. Schwarte-Waldhoff [et al.] // Proc. Natl. Acad. Sci. USA. – 2000. – № 97. – Р. 9624-9629.

4. 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.

5. Shtabinskaya, T.T. Prognostic significance of endoglin expression in colon adenocarcinoma with synchronous metastases / T.T. Shtabinskaya, M. Bodnar // Научният потенциал на света – 2017: материали XIII Междунар. науч.- практ. конф., София, 15-22 Септември, 2017. – София, 2017. – P. 14-16.