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.
Bibliographical noteFunding Information:
We thank the VCFG for providing the shRNA constructs and Lisa Horvath (Garvan Institute of Medical Research) for providing the SFRP4 antibody used for IHC. We also acknowledge David Faulkner (Peter MacCallum Cancer Centre Department of Pathology) for assistance with the CEA and CA19-9 testing.
This research was supported by funding from the Peter Mac Foundation (RB), VCA (Early Career Seed Grant to RB), No Stomach For Cancer Foundation (AB/RB), NHMRC grants ID454584 (AB), ID1030980 (AB), The Li Ka Shing Foundation (AB) and philanthropic funding from the Estate of George Wilson and an anonymous donor.
© 2020, The Author(s).
All Science Journal Classification (ASJC) codes
- Cancer Research