دورية أكاديمية
Serial Analysis of Gene Mutations and Gene Expression during First-Line Chemotherapy against Metastatic Colorectal Cancer: Identification of Potentially Actionable Targets within the Multicenter Prospective Biomarker Study REVEAL
| العنوان: | Serial Analysis of Gene Mutations and Gene Expression during First-Line Chemotherapy against Metastatic Colorectal Cancer: Identification of Potentially Actionable Targets within the Multicenter Prospective Biomarker Study REVEAL |
|---|---|
| المؤلفون: | Jörg Kumbrink, Lisa Bohlmann, Soulafa Mamlouk, Torben Redmer, Daniela Peilstöcker, Pan Li, Sylvie Lorenzen, Hana Algül, Stefan Kasper, Dirk Hempel, Florian Kaiser, Marlies Michl, Harald Bartsch, Jens Neumann, Frederick Klauschen, Michael von Bergwelt-Baildon, Dominik Paul Modest, Arndt Stahler, Sebastian Stintzing, Andreas Jung, Thomas Kirchner, Reinhold Schäfer, Volker Heinemann, Julian W. Holch |
| المصدر: | Cancers, Vol 14, Iss 15, p 3631 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | metastatic colorectal cancer, next generation sequencing, gene expression signature, biomarker, liquid biopsy, secondary resistance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Most metastatic colorectal cancer (mCRC) patients succumb to refractory disease due to secondary chemotherapy resistance. To elucidate the molecular changes associated with secondary resistance, we recruited 64 patients with mCRC and hepatic metastases before standard first-line chemotherapy between 2014 and 2018. We subjected DNA from primary tumor specimens (P), hepatic metastasis specimens after treatment (M), and liquid biopsies (L) taken prior to (pre), during (intra), and after (post) treatment to next generation sequencing. We performed Nanostring expression analysis in P and M specimens. Comparative bioinformatics and statistical analysis revealed typical mutational patterns with frequent alterations in TP53, APC, and KRAS in P specimens (n = 48). P and pre-L (n = 42), as well as matched P and M (n = 30), displayed a similar mutation spectrum. In contrast, gene expression profiles classified P (n = 31) and M (n = 23), distinguishable by up-regulation of immune/cytokine receptor and autophagy programs. Switching of consensus molecular subtypes from P to M occurred in 58.3% of cases. M signature genes SFRP2 and SPP1 associated with inferior survival, as validated in an independent cohort. Molecular changes during first-line treatment were detectable by expression profiling rather than by mutational tumor and liquid biopsy analyses. SFRP2 and SPP1 may serve as biomarkers and/or actionable targets. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2072-6694 |
| العلاقة: | https://www.mdpi.com/2072-6694/14/15/3631Test; https://doaj.org/toc/2072-6694Test |
| DOI: | 10.3390/cancers14153631 |
| الوصول الحر: | https://doaj.org/article/ac551b05f43141138488488ec5ebd79fTest |
| رقم الانضمام: | edsdoj.551b05f43141138488488ec5ebd79f |
| قاعدة البيانات: | Directory of Open Access Journals |
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