Expression of individual members of the TGF-β/SMAD signalling pathway in the progression and survival of patients with colorectal carcinoma

Abstract

Current knowledge of tumor biology offers many "targets" for therapeutic intervention. The molecular basis of many processes that play a role in the pathogenesis of colorectal cancer has been identified. One part of colorectal cancer clinical trials is focused on testing substances in a group of patients with tumors in which the TGF-β signalling pathway is hyperactivated. The TGF-β/SMAD signalling pathway members are considered important markers; however, genetic, proteomic, or metabolomic analyses still yield controversial results. According to our results, TGF-βRII, and SMAD4 can be used in monitoring CRC progression. With increasing CRC stage, TGF-βRII expression decreases and SMAD4 expression increases. The patients with TGF-βRII expression lower than 700 pg/ml had a slightly lower survival time (28.103 months) than patients with higher TGF-βRII expression (31.620 months). Conversely, patients with SMAD4 expression lower than 200 pg/ml had a higher survival rate (30.979 months) than patients with higher expression (26.316 months). Regarding TGF-β1 expression, the patient´s survival assessment determined no significant difference between patients with high or low tissue TGF-β1 expression. A personalized approach and consideration of a wide range of factors are important when using these markers in treatment assessment.

Keywords: Colorectal carcinoma; TGF-β/SMAD signalling pathway.

Fig. 1

Expression of genes for TGF-βRII (A), TGF-β1 (B), SMAD4 (C) in tissues of CRC patients compared with other types of GIT tumors (MTG: Malignant tumor group; BTG: Benign tumor group; TPM: Transcript per million; COAD: Colorectal Adenocarcinoma; ESCA: Esophageal carcinoma; LIHC: Liver hepatocellular carcinoma; PAAD: Pancreatic adenocarcinoma; STAD: Stomach adenocarcinoma; *: p < 0,05).

Fig. 2

Gene expression for TGF-βR2 (A), TGF-β1 (B), and SMAD4 (C) in CRC patients divided into different clinical stages (TPM: Transcript per million).

Fig. 3

Survival curves as a function of gene expression for TGF-βRII (A), TGF-β1 (B), and SMAD4 (C) in CRC patients (TPM: Transcript per million).

Fig. 4

Expression of tissue TGF-βRII (I), TGF-β1 (II), and SMAD4 (III) in CRC patients divided according to TNM classification markers and gender (A-males and B-females) patients.

Fig. 5

Kaplan-Meier survival tests based on the expression of individual TGF-β markers.

Fig. 6

SMAD4 proteins (60 kDa) confirmed in patients divided according to TNM classification. (BTG: Benign tumor group). *Patients whose SMAD 4 expression most closely reflects the group of patients at the given stage were selected.