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High expression of TFEB is associated with aggressive clinical features in colorectal cancer.

ABSTRACT: Objectives:The transcription factor EB (TFEB), a member of the micropthalmia family, has been found to be associated with autophagy and upregulated in some kinds of tumors. However, very few studies focused on TFEB in colorectal cancer (CRC). TFEB expression status and its relevance to clinical features in CRC would be analyzed in this study. Materials and methods:Real-time PCR, Western blot, and immunohistological staining were used to evaluate TFEB expression in CRC tissues and adjacent normal tissues, and the role of TFEB in CRC cell lines was investigated in vitro and in vivo. Results:TFEB was expressed at lower level in CRC tissues than normal in both mRNA and protein level. However, there were significantly positive correlations between TFEB expression in cancer tissues and malignant progression of CRC. Cancers with TFEB overexpression always had deeper infiltration and higher lymphatic metastasis rate. Furthermore, patients with high TFEB levels always had poor survival, and higher TFEB expression could be a predictor of survival in multivariate analysis. Meanwhile, knockdown TFEB by shRNA or knockout TFEB by sgRNA in CRC cell lines could significantly inhibit cell proliferation and migration in amino acid-free medium. In addition, we found a positive relationship between TFEB and Beclin1 expression, and silencing TFEB inhibited Beclin1 expression in CRC cells. Conclusion:TFEB expression correlated with aggressive clinical features in CRC, and higher TFEB expression could be a prognostic factor and potential treatment target of CRC.

SUBMITTER: Liang J

PROVIDER: S-EPMC6239122 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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High expression of TFEB is associated with aggressive clinical features in colorectal cancer.

Liang Jing J Jia Xinfeng X Wang Kun K Zhao Niankun N

OncoTargets and therapy 20181113

<h4>Objectives</h4>The transcription factor EB (TFEB), a member of the micropthalmia family, has been found to be associated with autophagy and upregulated in some kinds of tumors. However, very few studies focused on TFEB in colorectal cancer (CRC). TFEB expression status and its relevance to clinical features in CRC would be analyzed in this study.<h4>Materials and methods</h4>Real-time PCR, Western blot, and immunohistological staining were used to evaluate TFEB expression in CRC tissues and ...[more]

PMID: 30519051

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Project description:Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, ?-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.

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High expression of TFEB is associated with aggressive clinical features in colorectal cancer.

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High expression of TFEB is associated with aggressive clinical features in colorectal cancer.

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