High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases

British Journal of Cancer
Moritz J StrowitzkiMartin Schneider

Abstract

Patients with borderline resectable colorectal liver metastases (CRLM) frequently receive neoadjuvant chemotherapy (NC) to reduce tumour burden, thus making surgical resection feasible. Even though NC can induce severe liver injury, most studies investigating tissue-based prognostic markers focus on tumour tissue. Here, we assessed the prognostic significance of pyruvate-dehydrogenase-kinase isoenzyme 4 (PDK4) within liver tissue of patients undergoing surgical resection due to CRLM. Transcript levels of hypoxia-adaptive genes (such as PDK isoenzymes) were assessed in the tissue of healthy liver, corresponding CRLM, healthy colon mucosa and corresponding tumour. Uni- and multivariate analyses were performed. Responses to chemotherapy upon up- or down-regulation of PDK4 were studied in vitro. PDK4 expression within healthy liver tissue was associated with increased overall survival and liver function following surgical resection of CRLM. This association was enhanced in patients with NC. PDK4 expression in CRLM tissue did not correlate with overall survival. Up-regulation of PDK4 increased the resistance of hepatocytes and colon cancer cells against chemotherapy-induced toxicity, whereas knockdown of PDK4 enhanced chemotherapy-a...Continue Reading

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Citations

Aug 4, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Moritz J StrowitzkiMartin Schneider
Mar 26, 2021·Cancer Management and Research·Amy BodyEva Segelov
Mar 20, 2021·Bioscience Reports·Xiuxiu WangHongmin Li
Mar 31, 2021·JCI Insight·Moritz J StrowitzkiMartin Schneider

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Datasets Mentioned

BETA
GS5166

Methods Mentioned

BETA
surgical resection
FCS
Transfection
ELISA
PCR
fluorescence microscopy

Software Mentioned

ImageJ
SPSS
GraphPad Prism

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