{"id":2688,"date":"2021-02-18T11:56:27","date_gmt":"2021-02-18T10:56:27","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2688"},"modified":"2021-09-05T11:58:35","modified_gmt":"2021-09-05T09:58:35","slug":"becn1-and-brca1-deficiency-sensitizes-ovarian-cancer-to-platinum-therapy-and-confers-better-prognosis","status":"publish","type":"post","link":"http:\/\/www.isidorolab.com\/public\/index.php\/2021\/02\/18\/becn1-and-brca1-deficiency-sensitizes-ovarian-cancer-to-platinum-therapy-and-confers-better-prognosis\/","title":{"rendered":"BECN1 and BRCA1 Deficiency Sensitizes Ovarian Cancer to Platinum Therapy and Confers Better Prognosis"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"2688\" class=\"elementor elementor-2688\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-5b38c1b2 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"5b38c1b2\" data-element_type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-6a8b49c3\" data-id=\"6a8b49c3\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-3bee1214 elementor-widget elementor-widget-text-editor\" data-id=\"3bee1214\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Salwa+A&amp;cauthor_id=33670664\">Amreen Salwa<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ferraresi+A&amp;cauthor_id=33670664\">Alessandra Ferraresi<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Chinthakindi+M&amp;cauthor_id=33670664\">Menaka Chinthakindi<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Vallino+L&amp;cauthor_id=33670664\">Letizia Vallino<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Vidoni+C&amp;cauthor_id=33670664\">Chiara Vidoni<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-1\"> 1 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Dhanasekaran+DN&amp;cauthor_id=33670664\">Danny N Dhanasekaran<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Isidoro+C&amp;cauthor_id=33670664\">Ciro Isidoro<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33670664\/#affiliation-1\"> 1<\/a><\/sup><\/p>\n<p>\u00a0<\/p>\n\n<h3 class=\"wp-block-heading\">Affiliations<\/h3>\n\n<p><sup>1<\/sup> Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale &#8220;A. Avogadro&#8221;, Via Solaroli 17, 28100 Novara, Italy.<\/p>\n<p><sup>2<\/sup> Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.<\/p>\n<p>\u00a0<\/p>\n\n<p>PMID: <strong>33670664<\/strong><\/p>\n<p>PMCID: <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/pmc7922320\/\" target=\"_blank\" rel=\"noreferrer noopener\">PMC7922320<\/a><\/p>\n<p>DOI: <a href=\"https:\/\/doi.org\/10.3390\/biomedicines9020207\" target=\"_blank\" rel=\"noreferrer noopener\">10.3390\/biomedicines9020207<\/a><\/p>\n<p>\u00a0<\/p>\n<hr \/>\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n<p><strong>Background:<\/strong> <em>BRCA1, BECN1<\/em> and <em>TP53<\/em> are three tumor suppressor genes located on chromosome 17 and frequently found deleted, silenced, or mutated in many cancers. These genes are involved in autophagy, apoptosis, and drug resistance in ovarian cancer. Haploinsufficiency or loss-of-function of either <em>TP53<\/em>, <em>BRCA1<\/em> or <em>BECN1<\/em> correlates with enhanced predisposition to cancer development and progression, and chemoresistance. Expectedly, the combined altered expression of these three tumor suppressor genes worsens the prognosis of ovarian cancer patients. However, whether such a genotypic pattern indeed affects the chemo-responsiveness to standard chemotherapy thus worsening patients&#8217; survival has not been validated in a large cohort of ovarian cancer patients.<\/p>\n\n<p><strong>Aim:<\/strong> We interrogated datasets from the TCGA database to analyze how the expression of these three tumor suppressor genes impacts on the clinical response to platinum-based chemotherapy thus affecting the survival of ovarian cancer patients.<\/p>\n\n<p><strong>Results and conclusion:<\/strong> Compared to EOC with homozygous expression of <em>BECN1<\/em> and <em>BRCA1<\/em>, tumors expressing low mRNA expression of these two tumor suppressor genes (either because of shallow (monoallelic) co-deletion or of promoter hypermethylation), showed higher sensitivity to platinum-based therapies and were associated with a better prognosis of ovarian cancer-bearing patients. This outcome was independent of <em>TP53<\/em> status, though it was statistically more significant in the cohort of patients with mutated <em>TP53<\/em>. Thus, sensitivity to platinum therapy (and probably to other chemotherapeutics) correlates with low expression of a combination of critical tumor suppressor genes. Our study highlights the importance of thoroughly assessing the genetic lesions of the most frequently mutated genes to stratify the patients in view of a personalized therapy. More importantly, the present findings suggest that targeting the function of both <em>BECN1<\/em> and <em>BRCA1<\/em> could be a strategy to restore chemosensitivity in refractory tumors.<\/p>\n<p>\u00a0<\/p>\n<p>\u00a0<\/p>\n\n<p><strong>Keywords:<\/strong> apoptosis; autophagy; chemoresistance; epigenetics; genome sequencing; ovarian cancer; personalized medicine; prognosis; tumor suppressor genes.<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t<div style='text-align:center' class='yasr-auto-insert-visitor'><!--Yasr Visitor Votes Shortcode--><div id='yasr_visitor_votes_06c964977d983' class='yasr-visitor-votes'><div class=\"yasr-custom-text-vv-before yasr-custom-text-vv-before-2688\">Clicca per votare questo articolo!<\/div><div id='yasr-vv-second-row-container-06c964977d983'\r\n                                        class='yasr-vv-second-row-container'><div id='yasr-visitor-votes-rater-06c964977d983'\r\n                                      class='yasr-rater-stars-vv'\r\n                                      data-rater-postid='2688'\r\n                                      data-rating='0'\r\n                                      data-rater-starsize='32'\r\n                                      data-rater-readonly='false'\r\n                                      data-rater-nonce='bb8f69d06e'\r\n                                      data-issingular='false'\r\n                                    ><\/div><div class=\"yasr-vv-stats-text-container\" id=\"yasr-vv-stats-text-container-06c964977d983\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" width=\"20\" height=\"20\"\r\n                                   class=\"yasr-dashicons-visitor-stats\"\r\n                                   data-postid=\"2688\"\r\n                                   id=\"yasr-stats-dashicon-06c964977d983\">\r\n                                   <path d=\"M18 18v-16h-4v16h4zM12 18v-11h-4v11h4zM6 18v-8h-4v8h4z\"><\/path>\r\n                               <\/svg><span id=\"yasr-vv-text-container-06c964977d983\" class=\"yasr-vv-text-container\">[Total: <span id=\"yasr-vv-votes-number-container-06c964977d983\">0<\/span>  Average: <span id=\"yasr-vv-average-container-06c964977d983\">0<\/span>]<\/span><\/div><div id='yasr-vv-loader-06c964977d983' class='yasr-vv-container-loader'><\/div><\/div><div id='yasr-vv-bottom-container-06c964977d983' class='yasr-vv-bottom-container'><\/div><\/div><!--End Yasr Visitor Votes Shortcode--><\/div>","protected":false},"excerpt":{"rendered":"<p>Amreen Salwa\u00a0 1 ,\u00a0Alessandra Ferraresi\u00a0 1 ,\u00a0Menaka Chinthakindi\u00a0 1 ,\u00a0Letizia Vallino\u00a0 1 ,\u00a0Chiara Vidoni\u00a0 1 ,\u00a0Danny N Dhanasekaran\u00a0 2 ,\u00a0Ciro Isidoro\u00a0 1 \u00a0 Affiliations 1 Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale &#8220;A. Avogadro&#8221;, Via Solaroli 17, 28100 Novara, Italy. 2 Stephenson Cancer Center, The University of Oklahoma Health Sciences&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"yasr_overall_rating":0,"yasr_post_is_review":"","yasr_auto_insert_disabled":"","yasr_review_type":"","footnotes":""},"categories":[136],"tags":[55],"class_list":["post-2688","post","type-post","status-publish","format-standard","hentry","category-paper","tag-cancer"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\r\n<title>BECN1 and BRCA1 Deficiency Sensitizes Ovarian Cancer to Platinum Therapy and Confers Better Prognosis - IsidoroLab<\/title>\r\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\r\n<link rel=\"canonical\" href=\"http:\/\/www.isidorolab.com\/public\/index.php\/2021\/02\/18\/becn1-and-brca1-deficiency-sensitizes-ovarian-cancer-to-platinum-therapy-and-confers-better-prognosis\/\" \/>\r\n<meta property=\"og:locale\" content=\"it_IT\" \/>\r\n<meta property=\"og:type\" content=\"article\" \/>\r\n<meta property=\"og:title\" content=\"BECN1 and BRCA1 Deficiency Sensitizes Ovarian Cancer to Platinum Therapy and Confers Better Prognosis - IsidoroLab\" \/>\r\n<meta property=\"og:description\" content=\"Amreen Salwa\u00a0 1 ,\u00a0Alessandra Ferraresi\u00a0 1 ,\u00a0Menaka Chinthakindi\u00a0 1 ,\u00a0Letizia Vallino\u00a0 1 ,\u00a0Chiara Vidoni\u00a0 1 ,\u00a0Danny N Dhanasekaran\u00a0 2 ,\u00a0Ciro Isidoro\u00a0 1 \u00a0 Affiliations 1 Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale &#8220;A. 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