Meta-analysis of Osteopontin splice variants in cancer

Abstract

Background The cytokine Osteopontin is a mediator of tumor progression and cancer metastasis. In 2006, we reported that (in addition to the full-length form -a) splice variants of Osteopontin (forms -b and -c) are produced selectively by transformed cells. Through June 2021, 36 PubMed-indexed journal articles have studied Osteopontin splice variants in various cancer patients. Methods Applying a categorical approach previously developed by us, here we conduct a meta-analysis of the pertinent literature. We supplement this with evaluation of the relevant entries in the TSVdb database, which focusses on splice variant expression, thus including the additional variants -4 and -5. The analysis covers 5886 patients across 15 tumors from the literature and 10,446 patients across 33 tumors from TSVdb. Results The database yields positive results more frequently than the categorical meta-analysis. The two sources are in agreement on the elevation of OPN-a, OPN-b, and OPN-c in lung cancer and the elevation of OPN-c in breast cancer as compared to healthy tissue. Specific splice variants are associated with grade, stage, or patient survival pertaining to various cancers. Conclusions There are cases of persisting discrepancies, which require further investigation to clarify the Osteopontin splice variant utilization, so that their diagnostic, prognostic and potentially predictive potential can be brought to fruition.

Expression pattern of osteopontin isoforms in malignant melanoma cell lines

“…A recent comprehensive meta‐analysis of studies on OPN variants highlighted the association of specific splice variants with tumor grade, stage, or patient survival in various cancers. 11 However, in the case of MM, the only available study to date is our previous investigation focusing on five OPN splice variants ( OPNa , OPNb , OPNc , OPN4 , and OPN5 ) and their correlation with clinicopathological features of patients’ tumor tissues. 16 The present study aimed to analyze the relative gene expression levels of OPN isoforms in cell lines derived from primary and MM tissues and explore the association with clinicopathological parameters and invasive capacity.…”

“…Besides these variants, four additional isoforms have been described for OPN5 (OPN5b, OPN5c, OPN5d, and OPN5e). 10 , 11 , 12 Exons 6 and 7 encode over 80% of the OPN protein, which contains the region responsible for interacting with integrin receptors. Integrins are cell‐surface transmembrane heterodimer receptors, which are formed through noncovalent binding of an α and a β subunits, of which there are 18 and eight variants, respectively.…”

Crossroads: the role of biomarkers in the management of lumps in the breast

“…Circumstantial support comes from the observation of total OPN (4 studies, 172 patients [18]) or OPN-c (3 studies, 45 patients [19]) in the progression of premalignant lesions, and from increasing OPN-c blood levels with DCIS progression (67 patients [20]). Currently available tests are described for their basis, their purpose, and the target population they serve.…”

Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

“…The different splice variants including osteopontin-a, -b, and -c, are expressed differentially in cancers [ 40 , 41 ]. A meta-analysis based on data in published literature supplemented with data from the TSVdb concluded that in lung cancer, OPN-a, OPN-b, and OPN-c were increased in comparison to normal tissue, while in breast cancer, OPN-c was elevated [ 42 ].…”

“…The different splice variants including osteopontin-a, -b, and -c, are expressed differentially in cancers [40,41]. A meta-analysis based on data in published literature supplemented with data from the TSVdb concluded that in lung cancer, OPN-a, OPN-b, and OPN-c were increased in comparison to normal tissue, while in breast cancer, OPN-c was elevated [42]. Within the region encoded by exons 6 and 7 is a conserved Arg-Gly-Asp (RGD) sequence that interacts with αvb1, αvb3, and αvb5 integrins, allowing binding to various components of the extracellular matrix as well as some cell types.…”