Biology subjects

Hoppe, S.

Publications and source records attributed to Hoppe, S..

3 recordsLinked to original sources

bioRxiv2025

Esophageal adenocarcinoma relapse after chemoradiation is dominated by a basal-like subtype

Neoadjuvant chemoradiation therapy (RCT) is a frequently used treatment regimen for esophageal adenocarcinoma (EAC); however, the response varies dramatically, and resistance is a clinical challenge. We aimed to identify the molecular mechanisms underlying RCT resistance. We established a mouse xenograft RCT model with human EAC cell lines representing different response groups, and tested enhanced genomic instability as a potential evolutionary modulator by reducing BRCA2 function. Xenografts that relapsed after RCT displayed upregulation of stress response keratins, including KRT6 and KRT16 connected with a basal-like transcriptomic/ proteomic phenotype. We screened our cohort of 728 patients with EAC and found significantly shorter overall survival for patients with KRT6-high tumors, driven by patients receiving neoadjuvant treatment. Overall, we identified a basal-like cell state in EAC that reflects RCT relapse. The basal-like subtype is a marker of treatment failure, providing a new avenue for translational research to overcome RCT resistance.

cancer biology↗

bioRxiv2024

Gene expression adaptation of metastases to their host tissue

The adaptation of metastatic cells to their host tissue critically determines the pathogenicity of a cancer and therefore patient survival. Yet, it remains elusive to what extent the host environment drives gene expression programs in metastatic cells. Here we identify adaptive mechanisms that enable metastases to establish themselves in a novel tissue context. We performed single-cell RNA-sequencing on malignant and benign tissue samples from untreated donors with colorectal adenocarcinoma and liver metastasis to deduce tissue adaptive expression patterns. A novel computational approach identified genes and pathways that consistently adapted to the host tissue at the transition from the primary tumor to the paired metastasis across donors. This analysis revealed that the majority of expression changes in the metastasis reflect an expression signature reminiscent of benign liver epithelial cells. Cellular processes adapting to the liver environment include basic cellular functions such as energy metabolism, as well as tissue-specific pathways such as the regulation of lipid metabolism by PPAR-. These adaptations potentially increase the pathogenicity of the metastatic cells and may provide new therapeutic strategies.

cancer biology↗

bioRxiv2024

Single cell analysis of Barrett's esophagus and carcinoma reveals cell types conferring risk via genetic predisposition

Inherited genetic variants contribute to Barretts esophagus (BE) and esophageal adenocarcinoma (EAC) but it is unknown which cell types are involved in this process. We performed single cell RNA-sequencing of BE, EAC and paired normal tissues and integrated data of a genome-wide association study to determine cell type-specific genetic risk and cellular processes that contribute to BE and EAC. The analysis revealed that EAC development is driven to a greater extent by local cellular processes than BE development. One cell type of BE origin (BE-EAC) and cellular processes that control the differentiation of columnar cells are of particular relevance for EAC development. Further, specific subtypes of fibroblasts and endothelial cells contribute to BE and EAC development, while dendritic cells and CD4+ memory T cells contribute exclusively to BE development. The diagnostic use of markers characterizing the identified cell types and cellular processes should be explored in future for EAC prediction.

cancer biology↗