3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Increased PTEN gene expression in patients with endometrial carcinoma from areas of high risk depleted uranium exposure

      brief-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Investigate PTEN gene expression and tumor aggressiveness in endometrial carcinoma specimens from patients living in either areas of depleted uranium [DU] pollution or unpolluted regions to determine any evidence for the effect of war pollution on the rising trends of cancer incidence in Iraq.

          Results

          Tumor PTEN gene expression was significantly increased in patients living in the areas of high risk DU exposure, in comparison to patient tumors from low risk areas [P = 0.001]. The age distribution between the potentially DU exposed (55.09 ± 1.24) and unexposed subjects 56.38 ± 1.18) was not significant [P = 0.45]. Endometrial carcinoma aggressiveness was equivalent in both subject groups, with no significant differences in either tumour grade and [P = 0.286] stage distribution [P = 0.98]. Finally, there were no significant differences between the potentially exposed and unexposed subjects with regard to cervical [P = 0.532] or to ovarian involvement [P = 0.518]. The results linked environmental war pollutants [DU] to alterations in PTEN gene expression in endometrial carcinoma. Furthermore, this finding may explain the overall increasing cancer trends observed in Iraq. Strategies should be considered for the therapeutic targeting of cancers with elevated PTEN gene expression to improve patient outlook.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Clinical statistics of gynecologic cancers in Japan

          Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve point five percent of ovarian cancer patients received neoadjuvant chemotherapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            LncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells

            Background Growth arrest-specific 5 (GAS5) was reported to be implicated and aberrantly express in multiple cancers. However, the expression and mechanism of action of GAS5 were largely poor understood in endometrial carcinoma. Results According to the result of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and flow cytometry analysis, we identified that GAS5 was down-regulated in endometrial cancer cells and stimulated the apoptosis of endometrial cancer cells. To investigate the expression of GAS5, PTEN and miR-103, RT-PCR was performed. And we found that the expression of PTEN was up-regulated when endometrial cancer cells overexpressed GAS5. The prediction of bioinformatics online revealed that GAS5 could bind to miR-103, which was further found to be regulated by GAS5. Finally, we found that miR-103 mimic could decrease the mRNA and protein levels of PTEN through luciferase reporter assay and western blotting, and GAS5 plasmid may reverse this regulation effect in endometrial cancer cells. Conclusion In summary, we demonstrate that GAS5 acts as an tumor suppressor lncRNA in endometrial cancer. Through inhibiting the expression of miR-103, GAS5 significantly enhanced the expression of PTEN to promote cancer cell apoptosis, and, thus, could be an important mediator in the pathogenesis of endometrial cancer.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing

              PTEN is a tumor suppressor that negatively regulates the PI3K-AKT signaling pathway, which is implicated in the pathogenesis of endometrial carcinoma. Sanger sequencing has been considered to be the gold standard for detection of PTEN sequence abnormalities. However, this approach fails to address the epigenetic mechanisms that contribute to functional PTEN loss. Using a study cohort of 154 endometrioid and non-endometrioid endometrial carcinomas, we performed full-length PTEN sequencing and PTEN immunohistochemistry on each tumor. PTEN sequence abnormalities were detected in a significantly lower proportion of cases (43%) than PTEN protein loss (64%, p= 0.0004). Endometrioid tumors had a significantly higher proportion of PTEN sequence abnormalities and PTEN protein loss than non-endometrioid tumors. Within the latter group, PTEN sequence abnormalities and PTEN protein loss were most frequent in undifferentiated carcinomas, followed by mixed carcinomas; they were least frequent in carcinosarcomas. Overall, at least one PTEN sequence abnormality was detected in each exon, and the greatest number of sequence abnormalities was detected in exon 8. Pure endometrioid tumors had a significantly higher frequency of sequence abnormalities in exon 7 than did the non-endometrioid tumors (p=0.0199). Importantly, no mutational hotspots were identified. While PTEN protein loss by immunohistochemistry was identified in 89% of cases with a PTEN sequence abnormality, PTEN protein loss was detected by immunohistochemistry in 44% of cases classified as PTEN wildtype by sequencing. For the first time, we demonstrate that PTEN immunohistochemistry is able to identify the majority of cases with functional PTEN loss. However, PTEN immunohistochemistry also detects additional cases with PTEN protein loss that would otherwise be undetected by gene sequencing. Therefore, for clinical purposes, immunohistochemistry appears to be a preferable technique for identifying endometrial tumors with loss of PTEN function.
                Bookmark

                Author and article information

                Contributors
                alaa.alshammari@uokufa.edu.iq
                hawhad1979@gmail.com
                liwaa.alkulabi@uokufa.edu.iq
                emadhatem8@gmail.com
                asadjanabi@uokufa.edu.iq
                Katherine.McAllister@qub.ac.uk , cathyz19@hotmail.com
                akeelyasseen@uokufa.edu.iq
                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                1756-0500
                29 October 2019
                29 October 2019
                2019
                : 12
                : 708
                Affiliations
                [1 ]GRID grid.442852.d, Department of Pathology and Forensic Medicine, Faculty of Medicine, , University of Kufa, ; Kufa, P.O. Box 21, Iraq
                [2 ]Al-Furat Al-Awsat Hospital, Kufa, Najaf Governorate, Iraq
                [3 ]Al-Diwaniya Gynecology and Pediatric Hospital, Al-Qadisiya Governorate, Iraq
                [4 ]ISNI 0000 0004 0374 7521, GRID grid.4777.3, Centre for Cancer Research and Cell Biology, , Queens University Belfast, ; Belfast, UK
                Article
                4756
                10.1186/s13104-019-4756-4
                6821011
                31665075
                2d9dab63-261d-4f1b-adf2-3eef92f56fd0
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 January 2019
                : 19 October 2019
                Categories
                Research Note
                Custom metadata
                © The Author(s) 2019

                Medicine
                depleted uranium,pten gene,endometrial carcinoma
                Medicine
                depleted uranium, pten gene, endometrial carcinoma

                Comments

                Comment on this article