The roles of p53 and XPO1 on colorectal cancer progression in Yemeni patients

Al-Adhraei, Mohammed Ali; Al-Salami, Eman; Poungvarin, Naravat; Suwannalert, Prasit

doi:10.21037/jgo.2019.01.17

Cited by 8 publications

(6 citation statements)

References 30 publications

(29 reference statements)

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“…In CRC, little is known about the overexpression of XPO1 in tissue samples and its association with histopathological features, NF-κB and Ki67. Our previous study concerned of p53, reported that the XPO1 positivity was associated with loss of p53 expression in CRC tumors with lymph node metastasis (Aladhraei et al, 2019). In the current study, we noticed a significant apparent of XPO1 overexpression in CRC tumor cells compared to the adjacent normal epithelium as it was reported in many other types of cancers such as esophageal (van der Watt et al, 2014), gastric (Subhash et al, 2018), lung (Gao et al, 2015), and ovarian (Noske et al, 2008) cancers, as well as leukemic cells (Kojima et al, 2013).…”

Section: Discussionsupporting

confidence: 77%

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Al-Adhraei

Al‐Thobhani

Poungvarin

et al. 2019

Asian Pac J Cancer Prev

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also known as chromosome region maintenance 1 (CRM1) protein, is involved in the homeostatic of nucleocytoplasmic transport of over 200 known cargos, most of them are tumor suppressor and cell cycle regulatory proteins such as p53, pRb, FOXOs, BRCA1/2 and inhibitor of NF-κB (Kau et al., 2004; Abstract Objectives: Exportin 1(XPO1), a nuclear exporter protein, has been gaining recognition in cancer progression and treatment. This study aimed to evaluate the association between the overexpression of XPO1 with NF-κB, Ki67 and clinicopathological characteristics in colorectal cancer (CRC) tissue samples and to explore the anti-proliferative effect of KPT-330, as XPO1 inhibitor, in colorectal cancer cell line. Methods: Forty CRC tissue samples were analyzed by immunostaining for the expressions of XPO1, NF-κB and Ki67 and then the anti-proliferative effect of the KPT-330 was also evaluated in HT29 colorectal cancer cell line. Results: XPO1 overexpression was observed in 52.5% of CRC and significantly apparent with strong intensity in tumor cells compared to the normal adjacent epithelium (P<0.001).Regarding to the histopathological characteristics, the XPO1 overexpression significantly associated with advanced tumor stages (P=0.049) and has great tendency towards moderate/poorly differentiated tumors. Although the XPO1 overexpression was strongly associated with high Ki67 expression (P=0.001), only Ki67 expression showed significant association with tumor size (P=0.012). No significant association was detected between the XPO1 overexpression and NF-κB, while the NF-κB positive expression was significantly associated with lymph node metastasis and Ki67 expression at P=0.027 and P= 0.007, respectively. The in vitro experiments showed a great impact of KPT-330, as XPO1 inhibitor, to inhibit cancer growth in dose and time dependent manner and significantly diminished the colony formation (P<0.001) of HT29 cells-associated with the expression of Ki67 (P<0.001). Conclusion: XPO1 overexpression and NF-κB expression may serve as potential biomarker associated with CRC pathogenesis and proliferation, while the KPT-330 is effectively inhibited-colon cancer growth in vitro. Further studies considering the prognostication role of XPO1 overexpression in CRC are required.

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Section: Discussionsupporting

confidence: 77%

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Al-Adhraei

Al‐Thobhani

Poungvarin

et al. 2019

Asian Pac J Cancer Prev

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“…In CRC, the modulation of the p53 protein level is commonly seen; its landmark sign and relation with clinicopathological properties are still doubtful. Although some studies have reported no relationship between p53 protein levels and clinicopathological properties, some studies have indicated that p53 expression is related to the metastatic period (Aladhraei et al, 2019). Nevertheless, Cao et al (2017) stated that the lack of p53 expression was reported in CRC tumors and related to a worse clinicopathological response ,including lymph node metastasis and progressive tumor development, because over 50% of human cancers present defects of function mutations in TP53gene.…”

Section: Resultsmentioning

confidence: 99%

Comparison of anticarcinogenic properties of Viburnum opulus and its active compound p-coumaric acid on human colorectal carcinoma

Karakurt¹,

Abuşoğlu²,

Arıtuluk³

2020

Turk J Biol

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Resistance to therapeutic agents and the highly toxic side effects of synthetic drugs has spurred new research in the treatment of colon cancer, which has high morbidity and mortality ratios. This study aims to clarify the molecular mechanisms of the anticarcinogenic properties of methanol extract of Viburnum opulus L. (EVO)and its main active compound, trans-p -coumaric acid ( p -CA), on human colon cancer cells (DLD-1, HT-29, SW-620, Caco-2) and healthy colon epithelial cells (CCD-18Co). The effects of EVO on controlled cell death (apoptosis) and the cell division cycle were determined by flow cytometry. Alteration in mRNA and protein expressions of switch genes in colorectal carcinoma (APC, MLH1, TP53, SMAD4, KRAS, and BRAF) were determined by qRT-PCR and Western blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLC analyses prove that p -CAis the main compound of EVO. EVO and p -CA inhibit the proliferation of human colon cancer cells DLD-1 and HT-29 in a dose-dependent manner. EVO increases apoptosis of DLD-1 cells and halts the cell cycle in the G2 stage in HT-29 cells. mRNA and protein expressions of p53 and SMAD-4 are upregulated, while BRAFs are downregulated. The results were directly proportional to p -CA. EVO and p -CA up- and downregulate switch genes and protein expressions of DLD-1 cells, which alter the expression of 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effects may be due to the presence of p -CA.

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“…In addition, if there is a product missense variation of the TP53 gene, the mutant protein product is relatively resistant to MDM2-mediated ubiquitination and accumulates in the nucleus of cancer cells, leading to overexpression of p53 [ 21 ]. There have been previous reports that p53 overexpression is related to poor survival or progression of CRC in patients [ 24 , 25 ]. In our study, we investigated the prognosis of CRC patients according to the status of p53 IHC and TP53 variations.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer

et al. 2022

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In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.

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The roles of p53 and XPO1 on colorectal cancer progression in Yemeni patients

Cited by 8 publications

References 30 publications

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Association of XPO1 Overexpression with NF-κB and Ki67 in Colorectal Cancer

Comparison of anticarcinogenic properties of Viburnum opulus and its active compound p-coumaric acid on human colorectal carcinoma

Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer

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