Prognostic significance of transforming growth factor beta (TGF-β) signaling axis molecules and E-cadherin in colorectal cancer

Lampropoulos, Pavlos; Zizi-Sermpetzoglou, Adamantia; Rizos, Spyros; Kostakis, Alkiviadis; Nikiteas, Nikolaos; Papavassiliou, Athanasios G.

doi:10.1007/s13277-012-0333-3

Cited by 32 publications

(38 citation statements)

References 40 publications

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“…Several of the studies suggested that the expression of TGF-β1 was also associated with decreased patient survival, which was consistent with previous findings [8,9]. The expression of TGF-βR2 [8,18] and Smad4 [8,20] was reported to be associated with increased patient survival in some reports. Hence, it appears that there is a certain trend to the findings.…”

Section: Discussionsupporting

confidence: 86%

“…These studies have similar findings in some respects. The expression of TGF-β1 was generally associated with poor prognostic features including high-grade histology, advanced T-stage, lymph node metastasis and distant metastases [8,18,19]. Several of the studies suggested that the expression of TGF-β1 was also associated with decreased patient survival, which was consistent with previous findings [8,9].…”

Section: Discussionsupporting

confidence: 82%

“…However, the results have not been satisfactory, at least not until now. Table 6 is a summary of recent studies, conducted to evaluate the association between TGF-β signaling molecules and clinicopathological parameters such as histologic grade of tumor, disease stage, the presence of lymph node metastasis and patient survival [8,9,18,19,20,21]. These studies have similar findings in some respects.…”

Section: Discussionmentioning

confidence: 87%

“…The expression of TGF-β1 was generally associated with poor prognostic features including high-grade histology, advanced T-stage, lymph node metastasis and distant metastases [8,18,19]. Several of the studies suggested that the expression of TGF-β1 was also associated with decreased patient survival, which was consistent with previous findings [8,9]. The expression of TGF-βR2 [8,18] and Smad4 [8,20] was reported to be associated with increased patient survival in some reports.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that an increased expression of TGF-β is associated with disease progression and reduced survival in patients with CRC [6,7,8,9]. However, most of these studies incorporated heterogeneous groups of CRCs at various locations with different stages or else had too few cases to be able to draw a definite conclusion.…”

Section: Introductionmentioning

confidence: 99%

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Low Expression of Transforming Growth Factor Beta-1 in Cancer Tissue Predicts a Poor Prognosis for Patients with Stage III Rectal Cancers

Chun

Jung

Choi³

et al. 2014

Oncology

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Objective: Transforming growth factor beta (TGF-β) plays an important role in tumorigenesis and metastasis. It works as a tumor suppressor in the normal colon, but acts as a cancer promoter during the late stages of colorectal carcinogenesis. High expression of TGF-β is known to be associated with advanced stages, tumor recurrence and decreased survival of patients. We investigated the expression of TGF-β and its signaling axis molecules and evaluated their prognostic significance in patients with stage III rectal cancers. Methods: Tissues from 201 cases of stage III rectal cancer were subjected to immunohistochemistry for TGF-β1, type II TGF-β receptor, Smad3, Smad4 and Smad7 proteins. The immunoactivities of these molecules were evaluated and the results were compared with clinicopathological variables including patient survival. Results: Low expression of TGF-β1 protein was correlated with a decreased disease-free survival in univariate Kaplan-Meier (p = 0.003) and multivariate Cox regression (HR 9.188 and 95% CI 1.256-67.198, p = 0.029) analyses. The loss of Smad4 protein expression was associated with a reduction in disease-free survival in the univariate analysis, but this finding was not significant after the multivariate analysis. Conclusion: Low expression of TGF-β1 protein is associated with a poor prognosis for patients with stage III rectal cancers.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Low Expression of Transforming Growth Factor Beta-1 in Cancer Tissue Predicts a Poor Prognosis for Patients with Stage III Rectal Cancers

Chun

Jung

Choi³

et al. 2014

Oncology

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Polycystin‐1 and polycystin‐2 are involved in the acquisition of aggressive phenotypes in colorectal cancer

Gargalionis

Korkolopoulou

Farmaki

et al. 2014

Intl Journal of Cancer

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The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student's t-test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log-rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR 5 1.016, p 5 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p 5 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression.Invasion and metastasis are responsible for 90% of cancerassociated mortality. While the role of biochemical signals in invasion and metastasis is well established, growing evidence reveals that mechanical signals also regulate cancer-cell

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Relationships Between SMAD3 Expression and Preoperative Fluoropyrimidine‐Based Chemoradiotherapy Response in Locally Advanced Rectal Cancer Patients

et al. 2015

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Prognostic significance of transforming growth factor beta (TGF-β) signaling axis molecules and E-cadherin in colorectal cancer

Cited by 32 publications

References 40 publications

Low Expression of Transforming Growth Factor Beta-1 in Cancer Tissue Predicts a Poor Prognosis for Patients with Stage III Rectal Cancers

Low Expression of Transforming Growth Factor Beta-1 in Cancer Tissue Predicts a Poor Prognosis for Patients with Stage III Rectal Cancers

Polycystin‐1 and polycystin‐2 are involved in the acquisition of aggressive phenotypes in colorectal cancer

Relationships Between SMAD3 Expression and Preoperative Fluoropyrimidine‐Based Chemoradiotherapy Response in Locally Advanced Rectal Cancer Patients

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