MicroRNAs as biomarkers for trastuzumab-based therapy in HER2-positive advanced oesophago-gastric cancer patients
Copyright © 2023 Lote, Mousoullou, Vlachogiannis, Lampis, Satchwell, Peckitt, Fong, Begum, Kidd, Cromarty, Gordon, Fribbens, Rao, Starling, Chau, Cunningham and Valeri..
Background: This study aimed to identify microRNAs (miRs) as circulating biomarkers of resistance to first-line trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients.
Methods: A high-throughput 1015 Exiqon miRCURY LNA™ microRNA inhibitor library screen was performed in trastuzumab-treated HER2-positive NCI-N87 and HER2-negative FLO-1 oesophago-gastric cancer cell lines. NanoString nCounter® miR analysis was performed in NCI-N87, FLO-1, and MAGIC trial (ISRCTN93793971) formalin-fixed paraffin-embedded (FFPE) oesophago-gastric cancer patient samples. MiR-148a-3p copies in plasma samples were quantified using digital droplet polymerase chain reaction (ddPCR) from HER2-positive oesophago-gastric cancer patients treated with standard-of-care trastuzumab-based therapy within the FOrMAT (NCT02112357) and PLATFORM (NCT02678182) clinical trials. The primary endpoints were overall survival (OS) for plasma miR-148a-3p HIGH (>median) versus LOW (≤median). The secondary endpoints were progression-free survival (PFS) and 3-month progression-free rates (PFRs) miR-148a-3p HIGH versus LOW. PLATFORM sensitivity analysis normalised miR-148a-3p (NmiR-148a-3p).
Results: The inhibition of miR-148a-3p reduced NCI-N87 relative cell viability (<0.6) and expression was high (>242) in NCI-N87 and HER2-positive MAGIC trial patients (n=5). Normalised-miR-148a-3p (NmiR-148a-3p) LOW versus HIGH demonstrated a statistically significant difference in 3-month PFRs (n=23; OR, 0.11 [0.02-0.78]; p=0.027; aOR, 0.03 [0.001-0.71], p=0.029) but no difference in OS or PFS. There was no statistically significant relationship between miR-148-3p LOW versus HIGH for OS (PLATFORM, n=62; hazard ratio [HR], 0.98 [0.57-1.66]; p=0.933; FOrMAT, n=8; HR, 0.54 [0.13-2.31]; p=0.322), PFS (n=62; HR, 1.08 [0.65-1.81]; p=0.759; FOrMAT, n=8; HR, 1.26 [0.31-5.07]; p=0.714), or PFRs (PLATFORM, n=31; odds ratio [OR], 0.67 [0.2-2.8]; p=0.577).
Conclusion: Normalised miR-148a-3p may be a relevant biomarker for trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Frontiers in oncology - 13(2023) vom: 08., Seite 1258365 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lote, Hazel [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Revised 14.12.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2023.1258365 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 Lote, Mousoullou, Vlachogiannis, Lampis, Satchwell, Peckitt, Fong, Begum, Kidd, Cromarty, Gordon, Fribbens, Rao, Starling, Chau, Cunningham and Valeri. | ||
| 520 | |a Background: This study aimed to identify microRNAs (miRs) as circulating biomarkers of resistance to first-line trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients | ||
| 520 | |a Methods: A high-throughput 1015 Exiqon miRCURY LNA™ microRNA inhibitor library screen was performed in trastuzumab-treated HER2-positive NCI-N87 and HER2-negative FLO-1 oesophago-gastric cancer cell lines. NanoString nCounter® miR analysis was performed in NCI-N87, FLO-1, and MAGIC trial (ISRCTN93793971) formalin-fixed paraffin-embedded (FFPE) oesophago-gastric cancer patient samples. MiR-148a-3p copies in plasma samples were quantified using digital droplet polymerase chain reaction (ddPCR) from HER2-positive oesophago-gastric cancer patients treated with standard-of-care trastuzumab-based therapy within the FOrMAT (NCT02112357) and PLATFORM (NCT02678182) clinical trials. The primary endpoints were overall survival (OS) for plasma miR-148a-3p HIGH (>median) versus LOW (≤median). The secondary endpoints were progression-free survival (PFS) and 3-month progression-free rates (PFRs) miR-148a-3p HIGH versus LOW. PLATFORM sensitivity analysis normalised miR-148a-3p (NmiR-148a-3p) | ||
| 520 | |a Results: The inhibition of miR-148a-3p reduced NCI-N87 relative cell viability (<0.6) and expression was high (>242) in NCI-N87 and HER2-positive MAGIC trial patients (n=5). Normalised-miR-148a-3p (NmiR-148a-3p) LOW versus HIGH demonstrated a statistically significant difference in 3-month PFRs (n=23; OR, 0.11 [0.02-0.78]; p=0.027; aOR, 0.03 [0.001-0.71], p=0.029) but no difference in OS or PFS. There was no statistically significant relationship between miR-148-3p LOW versus HIGH for OS (PLATFORM, n=62; hazard ratio [HR], 0.98 [0.57-1.66]; p=0.933; FOrMAT, n=8; HR, 0.54 [0.13-2.31]; p=0.322), PFS (n=62; HR, 1.08 [0.65-1.81]; p=0.759; FOrMAT, n=8; HR, 1.26 [0.31-5.07]; p=0.714), or PFRs (PLATFORM, n=31; odds ratio [OR], 0.67 [0.2-2.8]; p=0.577) | ||
| 520 | |a Conclusion: Normalised miR-148a-3p may be a relevant biomarker for trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HER2 | |
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a gastric cancer | |
| 650 | 4 | |a microRNA | |
| 650 | 4 | |a oesophageal adenocarcinoma | |
| 650 | 4 | |a trastuzumab | |
| 700 | 1 | |a Mousoullou, Florentia |e verfasserin |4 aut | |
| 700 | 1 | |a Vlachogiannis, George |e verfasserin |4 aut | |
| 700 | 1 | |a Lampis, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Satchwell, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Peckitt, Clare |e verfasserin |4 aut | |
| 700 | 1 | |a Fong, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Begum, Ruwaida |e verfasserin |4 aut | |
| 700 | 1 | |a Kidd, Shannon |e verfasserin |4 aut | |
| 700 | 1 | |a Cromarty, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Gordon, Anderley |e verfasserin |4 aut | |
| 700 | 1 | |a Fribbens, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Sheela |e verfasserin |4 aut | |
| 700 | 1 | |a Starling, Naureen |e verfasserin |4 aut | |
| 700 | 1 | |a Chau, Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Cunningham, David |e verfasserin |4 aut | |
| 700 | 1 | |a Valeri, Nicola |e verfasserin |4 aut | |
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