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

Abstract

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.

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

“…Using IHC study, Lampropoulos et al reported that there was an association of cancer-specific OS with high TGF-b, as well as low SMAD4, and pSMAD2/3 expression in 195 unrelated CRC specimens [33]. Conversely, Chun et al found contrary results regarding the prognostic role of SMAD protein [34]. The loss of SMAD4 protein expression was associated with a reduction in DFS [34].…”

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis

“…Nine studies were conducted in European countries (UK, Germany, Italy, Sweden, Poland, Greece and Bulgaria) and in the United States (US), and four were conducted in Asian countries (China, Japan and Korea) [21, 22, 25, 26]. All the eligible studies were published between 1995 and 2015.…”

“…All patients included in the eligible studies underwent surgical resection. Only one study investigated rectal cancer [22], and two investigated colon cancer [25, 27], whereas other studies investigated colorectal cancer. One study included stage III patients [22], and one study included stage I-III patients [23].…”

“…Of these 7 studies, 5 directly reported the HRs, while the other 2 studies provided survival curves. Two out of the 7 studies identified high expression of TGF-β as an indicator of poor prognosis in terms of DFS [22, 27], whereas others showed no significant difference.…”

“…Seven studies on TGF-β and DFS in CRC patients undergoing surgery were included in the meta-analysis [16, 17, 22, 25–28]. The combined HR of the 7 studies that evaluated the relationship of the high expression of TGF-β to DFS was 1.11 (95% CI: 1.03–1.19, Table 3, Fig.…”