Molecular profiles of response to neoadjuvant chemoradiotherapy in oesophageal cancers to develop personalized treatment strategies.

Abstract

Identification of molecular predictive markers of response to neoadjuvant chemoradiation could aid clinical decision-making in patients with localized oesophageal cancer. Therefore, we subjected pretreatment biopsies of 75 adenocarcinoma (OAC) and 16 squamous cell carcinoma (OSCC) patients to targeted next-generation DNA sequencing, as well as biopsies of 85 OAC and 20 OSCC patients to promoter methylation analysis of eight GI-specific genes, and subsequently searched for associations with histopathological response and disease-free (DFS) and overall survival (OS). Thereby, we found that in OAC, CSMD1 deletion (8%) and ETV4 amplification (5%) were associated with a favourable histopathological response, whereas SMURF1 amplification (5%) and SMARCA4 mutation (7%) were associated with an unfavourable histopathological response. KRAS (15%) and GATA4 (7%) amplification were associated with shorter OS. In OSCC, TP63 amplification (25%) and TFPI2 (10%) gene promoter methylation were associated with an unfavourable histopathological response and shorter DFS (TP63) and OS (TFPI2), whereas CDKN2A deletion (38%) was associated with prolonged OS. In conclusion, this study identified candidate genetic biomarkers associated with response to neoadjuvant chemoradiotherapy in patients with localized oesophageal cancer.

• Authors: Leonie K de Klerk, Ruben S A Goedegebuure, Nicole C T van Grieken, Johanna W van Sandick, Annemieke Cats, Jurrien Stiekema, Rosa T van der Kaaij, Arantza Farina Sarasqueta, Manon van Engeland, Maarten A J M Jacobs, Roy L J van Wanrooij, Donald L van der Peet, Aaron R Thorner, Henk M W Verheul, Victor L J L Thijssen, Adam J Bass, Sarah Derks
• Journal: Molecular oncology (Mol Oncol) Vol. 15 Issue 4 Pg. 901-914 (04 2021) ISSN: 1878-0261 [Electronic] United States
• PMID: 33506581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• GATA4 Transcription Factor
• GATA4 protein, human
• Glycoproteins
• KRAS protein, human
• Nuclear Proteins
• TP63 protein, human
• Transcription Factors
• Tumor Suppressor Proteins
• tissue-factor-pathway inhibitor 2
• SMURF1 protein, human
• Ubiquitin-Protein Ligases
• SMARCA4 protein, human
• DNA Helicases
• Proto-Oncogene Proteins p21(ras)

Topics

• Adenocarcinoma (drug therapy, genetics)
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (drug therapy, genetics)
• CpG Islands
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• DNA Helicases (genetics)
• DNA Methylation
• Disease-Free Survival
• Esophageal Neoplasms (drug therapy, genetics)
• Female
• GATA4 Transcription Factor (genetics)
• Glycoproteins (genetics)
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy
• Netherlands
• Nuclear Proteins (genetics)
• Precision Medicine
• Promoter Regions, Genetic
• Proto-Oncogene Proteins p21(ras) (genetics)
• Transcription Factors (genetics)
• Tumor Suppressor Proteins (genetics)
• Ubiquitin-Protein Ligases (genetics)