TY - JOUR A1 - Schrecker, Christopher A1 - Behrens, Sophia A1 - Schönherr, Rebecca A1 - Ackermann, Anne A1 - Pauli, Daniel A1 - Plotz, Guido A1 - Zeuzem, Stefan A1 - Brieger, Angela T1 - SPTAN1 expression predicts treatment and survival outcomes in colorectal cancer T2 - Cancers N2 - Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality. In a cohort of 189 patients with CRC, we recently showed that expression of the cytoskeletal scaffolding protein non-erythroid spectrin αII (SPTAN1) was lower in advanced metastatic tumours. The aim of the present study was to clarify the association of intratumoural SPTAN1 expression levels with treatment and survival outcomes in patients with CRC. The analysis was based on histologic assessment of SPTAN1 protein levels in our own CRC cohort, and transcriptome data of 573 CRC cases from The Cancer Genome Atlas (TCGA). We first establish that high intratumoural levels of SPTAN1 protein and mRNA associate with favourable survival outcomes in patients with CRC. Next, a response prediction signature applied to the TCGA data reveals a possible link between high SPTAN1 transcript levels and improved patient responses to FOLFOX chemotherapy. Complementary in vitro experiments confirm that SPTAN1 knockdown strains of the colon cancer cell lines HT-29, HCT116 mlh1-2 and Caco-2 are less responsive to FOLFOX chemotherapy compared with SPTAN1-proficient control strains. Taken together, we identify SPTAN1 as a novel prognostic biomarker in CRC and show that SPTAN1 expression levels may predict patient responses to chemotherapy. These investigations illustrate how an affordable, histology-based diagnostic test could directly impact therapeutic decision-making at the bedside. KW - colorectal cancer KW - SPTAN1 KW - spectrin KW - cytoskeleton KW - metastasis KW - chemotherapy Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62485 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-624855 SN - 2072-6694 N1 - This work was supported by the Paul and Ursula Klein Foundation, as well as institutional funds from the University Hospital Frankfurt. Christopher Schrecker was supported by a personal grant from the German Research Foundation (Deutsche Forschungsgemeinschaft). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. VL - 13 IS - 14, art. 3638 SP - 1 EP - 19 PB - MDPI CY - Basel ER -