Insulin-like growth factor binding protein-7 (IGFBP7) is a gene identified as being low expressed in colorectal adenocarcinoma (CRC) cell lines. In the current study, we investigated the function of IGFBP7 in CRC by transfection studies. We found that IGFBP7 could inhibit cell growth, decrease soft agar colony formation activity and induce apoptosis in RKO and SW620 cells. Correlation analysis between the expression of IGFBP7 in CRC tissue and the prognosis in 218 patients showed that high expression of IGFBP7 was associated with favorable prognosis. Based on above results, we conclude that IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis.
Colorectal carcinoma with a micropapillary component (MP) is an exceptionally aggressive variant, but has never been investigated in terms of survival analysis. Thirty colorectal carcinomas with a MP were identified from a series of 221 colorectal carcinomas. Carcinomas with and without a MP were compared in terms of histologic and immunohistochemical markers. Colorectal carcinoma with a MP seemed to have a lower differentiation status, increased tumor budding, more frequent lymphovascular and perineural invasion, more frequent lymph node metastasis, higher tumor node metastasis (TNM) stage, and less nuclear beta-catenin staining (P<0.05). Further analysis revealed that the presence of a MP predicted more frequent lymph node metastasis in T1 and T2 stages but not in T3 and T4 stages. Five-year survival rates for patients with a MP and those without were 50% and 73%, respectively. Furthermore, in TNM stages I and II, but not in TNM stages III and IV, a MP was an unfavorable prognostic variable. A MP was demonstrated to be an independent unfavorable prognostic indicator in TNM stages I and II by the multivariate Cox proportional hazard model. Colorectal carcinoma with a MP should be distinguished from colorectal carcinoma of conventional histologic type.
SIRT3 is involved in aging-related diseases including cancer, but its role in prostate cancer and detailed regulatory function are not known. We found that SIRT3 was moderately down-regulated in prostate carcinomas. Overexpression of SIRT3 by lentiviral transfection inhibited prostate cancer growth both in vitro and in vivo, whereas knockdown of SIRT3 increased prostate tumor growth. Mechanistically, the tumor suppression effect of SIRT3 was achieved via its inhibition of the PI3K/Akt pathway. Notably, upregulation of SIRT3 suppressed the phosphorylation of Akt, leading to the ubiquitination and degradation of oncoprotein c-MYC; this could be attenuated by constitutive activation of PI3K/Akt signaling. Collectively, our results unveiled SIRT3's tumor suppressive function and the underlying mechanism in prostate cancer, which might provide therapeutic implications for the disease.
Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
Purpose: Classification based on a combination of molecular and pathologic predictors had never been done using hierarchical cluster analysis. For this purpose, we identified prognostic classification based on molecular predictors, pathologic and molecular predictors, and compared their respective prognostic efficacy together with that of tumor-node-metastasis (TNM) stage. Moreover, we investigated the prognostic significance of molecular classification in different TNM stage. Experimental Design: Six pathologic predictors (p) and 13 immunohistochemical predictors (m) were investigated in 221colorectal carcinomas. Unsupervised hierarchical clustering analysis was done to group the data. Survival analysis was done by Kaplan-Meier method and log-rank test, and by multivariate COX proportional hazard model. Results: Six pathologic predictors and four molecular predictors were of significant prognostic value (P V 0.05). One molecular predictor showed a trend toward significance (P = 0.085). Hierarchical clustering analysis was done based on different combinations (5p, 13m, 5m, 5p13m, and 5p5m), and distinct groups were produced except 5p (the TNM stage was excluded). Groups identified by 5m (P = 0.053) and 5p5m (P = 0.000) showed significant differences in prognosis. Groups identified by 5p5m andTNM stage were confirmed as the independent prognostic factors in a multivariate COX proportional hazard model. Moreover, groups identified by 5m could predict different prognoses in patients with stage II disease. Conclusions: Classification based on pathologic and immunohistochemical predictors is superior to that based only on molecular predictors on prognosis. Classification based on 5m could identify additional different prognoses in patients with stage II disease.Colorectal carcinoma is one of the leading causes of cancer mortality worldwide. Accurate prognosis analysis will greatly facilitate clinical decision of the best treatment plan and reduce the healthcare costs. Up to now, tumor-node-metastasis (TNM) staging has remained the most widely used system, but the patients operated on at the same TNM stage do not necessarily have the same prognosis. Recently, with the identification of numerous molecular predictors, a more accurate staging system is expected. There have been endeavors to build a prognostic evaluation system based on molecular markers. For example, Lyall et al. identified a prognostic immunohistochemical marker profile in 90 stage III colorectal carcinomas by unsupervised hierarchical cluster analysis of 23 markers (1). Knosel et al. evaluated 11 immunohistochemical markers in 270 colorectal carcinomas (2). However, because the pathologic and molecular predictors were always classified separately in the past (1 -5), it is still unknown whether the molecular staging system would yield more accurate prognosis analyses than the traditional TNM staging system.Unsupervised hierarchical clustering analysis is a common method to profile the gene expression or tissue microarray data. For example, it h...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.