{"id":8369,"date":"2024-12-17T11:09:14","date_gmt":"2024-12-17T10:09:14","guid":{"rendered":"https:\/\/www.hartwigmedicalfoundation.nl\/?p=8369"},"modified":"2024-12-17T11:09:14","modified_gmt":"2024-12-17T10:09:14","slug":"predicting-therapy-success-based-on-gene-expression","status":"publish","type":"post","link":"https:\/\/www.hartwigmedicalfoundation.nl\/en\/predicting-therapy-success-based-on-gene-expression\/","title":{"rendered":"Predicting therapy success based on gene expression\u00a0"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>In addition to Whole Genome Sequencing of DNA, Hartwig Medical Foundation performs Whole Transcriptome Sequencing of RNA. Researcher Marjolein Lansbergen utilized this data in her <\/strong><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39154856\/\" target=\"_blank\" rel=\"noreferrer noopener\"><strong>study<\/strong><\/a><strong> on pancreatic cancer<\/strong> <strong>and observed a clear correlation between gene expression and tumor sensitivity to a specific therapy.<\/strong>\u00a0<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>By Laura Nederveen<\/em>&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cWe categorized the tumors based on their gene expression profiles. In one group, the therapy was notably more effective than in the other,\u201d explains Marjolein Lansbergen. She is a PhD student affiliated with the Department of Medical Oncology and the Center of Experimental and Molecular Medicine at Amsterdam UMC and the Cancer Center Amsterdam. Her research focuses on metastatic pancreatic cancer under the supervision of medical oncologist Hanneke van Laarhoven and molecular biologist Maarten Bijlsma. The therapy in question is FOLFIRINOX, a widely used combination chemotherapy for this type of cancer. \u201cFOLFIRINOX is generally the best available therapy, but not everyone benefits from it,\u201d Lansbergen notes. For treatment selection, it is crucial to accurately predict which patients will respond positively to the treatment or not.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A tumor&#8217;s sensitivity to chemotherapy depends not only on DNA-level mutations; gene expression at the mRNA level plays a significant role. This expression dictates which genes are active and how the cell functions and responds to its environment\u2014including its response to therapy. Different cell types and tumors have unique gene expression profiles. Comparing these profiles allows researchers to classify tumors into (RNA) subgroups. Lansbergen aimed to devisea classification system that best predicts a patients chances to respond to chemotherapy. This would enable doctors to tailor treatment decisions by distinguishing different patient groups based on their gene expression profiles.&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-pullquote\"><blockquote><p>Marjolein Lansbergen<\/p><cite>&#8220;A tumor&#8217;s sensitivity to chemotherapy depends not only on DNA-level mutations; gene expression at the mRNA level plays a significant role&#8221;<\/cite><\/blockquote><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">For their study, Lansbergen and her colleagues collected tissue samples from patients prior to FOLFIRINOX treatment. This was done as part of the CPCT-02 study, a large-scale data collection initiative. Tumor size was monitored using CT scans, and survival data was recorded. The tissue samples were sent to Hartwig Medical Foundation for Whole Transcriptome Sequencing. Using the resulting mRNA data, Lansbergen tested several commonly used RNA subgroup classifiers.&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-pullquote\"><blockquote><p>Marjolein Lansbergen<\/p><cite>&#8220;For treatment selection, it is crucial to predict which patients will respond positively to the treatment&#8221;<\/cite><\/blockquote><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cUltimately, the classification between so-called classical and basal-like tumors aligned best with our data,\u201d Lansbergen explains. Basal-like tumors are generally more aggressive than classical tumors and resemble basal-like tumors found in breast and bladder cancers.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cWe observed clear differences in survival and tumor reduction between the two groups,\u201d says Lansbergen. Among patients treated with FOLFIRINOX, those with classical tumors lived longer than those with basal-like tumors. Classical tumors also showed a higher likelihood of ceasing growth compared to basal-like tumors. \u201cIt\u2019s gratifying that we were able to demonstrate this,\u201d Lansbergen says enthusiastically.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">One important gene that exhibited differential expression was <em>GATA6<\/em>. This gene can be measured not only at the RNA level but also at the protein level using immunohistochemical <em>GATA6 <\/em>staining. Lansbergen elaborates: \u201c<em>GATA6 <\/em>is a well-known marker associated with the classical tumor group. We observed that patients with high levels of <em>GATA6 <\/em>protein indeed lived longer on FOLFIRINOX compared to those with low levels of <em>GATA6<\/em>.\u201d&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-pullquote\"><blockquote><p>Marjolein Lansbergen<\/p><cite>\u201cWith this study, we demonstrate that gene expression profiles have the potential to support patients in making informed treatment decisions. Hopefully, this contributes to longer survival and fewer side effects.\u201d\u00a0<\/cite><\/blockquote><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">In metastatic pancreatic cancer, a relatively simple protein staining can therefore be used to indicate the RNA subgroup of a tumor, helping to predict the effectiveness of treatment. Lansbergen concludes: \u201cWith this study, we demonstrate that gene expression profiles have the potential to support patients and doctors in making informed treatment decisions. Hopefully, this contributes to longer survival and fewer side effects.\u201d&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>This research was recently published open access in <\/em><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39154856\/\" target=\"_blank\" rel=\"noreferrer noopener\"><em>Translational Research<\/em><\/a><em>.<\/em>&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>Hartwig Medical Foundation has built a database that includes RNAseq data from over 3,000 patients, encompassing the data used in the above study. An <\/em><a href=\"https:\/\/catalog.hartwigmedicalfoundation.nl\/\" target=\"_blank\" rel=\"noreferrer noopener\"><em>overview of all available data<\/em><\/a><em> can be found on Hartwig\u2019s website, where selections can be made based on various specifications such as primary tumor type, availability of RNA data and treatment type. An example display of this data overview is shown below. This tool was developed with support from the Dutch Cancer Society (KWF).<\/em>&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"655\" height=\"534\" src=\"https:\/\/www.hartwigmedicalfoundation.nl\/wp-content\/uploads\/2024\/12\/Scherm\u00adafbeelding-2024-12-17-om-09.28.38.png\" alt=\"\" class=\"wp-image-8367\" srcset=\"https:\/\/www.hartwigmedicalfoundation.nl\/wp-content\/uploads\/2024\/12\/Scherm\u00adafbeelding-2024-12-17-om-09.28.38.png 655w, https:\/\/www.hartwigmedicalfoundation.nl\/wp-content\/uploads\/2024\/12\/Scherm\u00adafbeelding-2024-12-17-om-09.28.38-300x245.png 300w\" sizes=\"auto, (max-width: 655px) 100vw, 655px\" \/><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>In addition to Whole Genome Sequencing of DNA, Hartwig Medical Foundation performs Whole Transcriptome Sequencing of RNA. Researcher Marjolein Lansbergen &hellip;<\/p>\n","protected":false},"author":3,"featured_media":8365,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[75,85,73,82,77],"tags":[],"class_list":["post-8369","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-hartwig-medical-database","category-learning-healthcare-system","category-personalized-treatment","category-research","category-scientific-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Predicting therapy success based on gene expression\u00a0 - Hartwig Medical Foundation<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.hartwigmedicalfoundation.nl\/en\/predicting-therapy-success-based-on-gene-expression\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Predicting therapy success based on gene expression\u00a0 - Hartwig Medical Foundation\" \/>\n<meta property=\"og:description\" content=\"In addition to Whole Genome Sequencing of DNA, Hartwig Medical Foundation performs Whole Transcriptome Sequencing of RNA. 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