SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence
- PDF / 1,416,520 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 20 Downloads / 175 Views
ORIGINAL ARTICLE
SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence Rita A. Busuttil1,2,3 · Joshy George4 · Colin M. House1 · Stephen Lade5 · Catherine Mitchell5 · Natasha S. Di Costanzo1 · Sharon Pattison6 · Yu‑Kuan Huang1,2,3 · Patrick Tan7,8 · Jae‑Ho Cheong9,10 · Sun Young Rha11 · Alex Boussioutas1,2,3 Received: 5 October 2020 / Accepted: 14 November 2020 © The Author(s) 2020
Abstract Objective Gastric cancer patients generally have a poor outcome, particularly those with advanced-stage disease which is defined by the increased invasion of cancer locally and is associated with higher metastatic potential. This study aimed to identify genes that were functional in the most fundamental hallmark of cancer, namely invasion. We then wanted to assess their value as biomarkers of gastric cancer progression and recurrence. Design Data from a cohort of patients profiled on cDNA expression arrays was interrogated using K-means analysis. This genomic approach classified the data based on patterns of gene expression allowing the identification of the genes most correlated with the invasion of GC. We evaluated the functional role of a key protein from this analysis in invasion and as a biomarker of recurrence after curative resection. Results Expression of secreted frizzled-related protein 4 (SFRP4) was identified as directly proportional to gastric cancer invasion. This finding was validated in multiple, independent datasets and its functional role in invasion was also confirmed using invasion assays. A change in serum levels of SFRP4 after curative resection, when coupled with AJCC stage, can accurately predict the risk of disease recurrence after curative therapy in an assay we termed PredictR. Conclusions This simple ELISA-based assay can help predict recurrence of disease after curative gastric cancer surgery irrespective of adjuvant therapy. The results require further evaluation in a prospective trial but would help in the rational prescription of cancer therapies and surveillance to prevent under or over treatment of patients after curative resection. Keyword SFRP4 · Gastric cancer · Invasion · Biomarker · Recurrence
Introduction Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s1012 0-020-01143-8.
Gastric cancer (GC) is the fifth most common cancer worldwide and the third-highest cause of cancer-related deaths [1]. In countries lacking established screening
* Alex Boussioutas [email protected]
6
Department of Medicine, University of Otago, Dunedin, New Zealand
7
Genome Institute of Singapore, Singapore, Singapore
8
Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
1
Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, VIC, Australia
2
Sir Peter MacC
Data Loading...
