Osteosarcoma tissues and cell lines from patients with differing serum alkaline phosphatase concentrations display minimal differences in gene expression patterns

Abstract

Serum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, although its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serum ALP concentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serum ALP concentration. No differences in gene expression patterns were noted between tumours or cell lines with differing serum ALP concentration using a gene-specific two-sample t-test. Using a more sensitive empirical Bayes procedure, defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was increased in both the tissue and cell lines of the normal ALP group. Using quantitative PCR (qPCR), differences in DCUN1D1 expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serum ALP concentrations are consistent with previous studies suggesting serum ALP concentration is not associated with intrinsic differences of osteosarcoma cells.

A Scoring System for Predicting Neoadjuvant Chemotherapy Response in Primary High‐Grade Bone Sarcomas: A Multicenter Study

“…ALP has been shown to be produced directly by human osteosarcoma cells, and its level can be increased in patients with osteosarcoma 33 . Given the disagreement regarding ALP as a prognostic indicator for osteosarcoma in previous studies, recent studies have reassessed the enzyme as a tumor marker and prognostic predictor, and these rigorous studies have reaffirmed the predictive value of elevated ALP for poor prognosis in patients with osteosarcoma 5,34–36 . In our study, ALP was a predictive factor of good response, but the weight was lower than that of other factors.…”

“…33 Given the disagreement regarding ALP as a prognostic indicator for osteosarcoma in previous studies, recent studies have reassessed the enzyme as a tumor marker and prognostic predictor, and these rigorous studies have reaffirmed the predictive value of elevated ALP for poor prognosis in patients with osteosarcoma. 5,[34][35][36] In our study, ALP was a predictive factor of good response, but the weight was lower than that of other factors. ALP is generally not considered a prognostic factor for ES and UPS.…”

An evaluation of TAZ and YAP crosstalk with TGFβ signalling in canine osteosarcoma suggests involvement of hippo signalling in disease progression

“…Specifically, OSA cells derived from canine patients with differing serum ALP levels displayed no differences in migration, invasion and chemosensitivity when evaluated in vitro [ 43 ]. Similarly, Rodrigues and colleagues reported that serum ALP is not associated with specific gene expression patterns or intrinsic differences between patient-derived OSA cells [ 44 ]. Yet, different gene expression profiles were shown to be useful in separating canine OSA patients into short and long-term survivors [ 45 ].…”

The Prognostic Role of Preoperative Hematological and Inflammatory Indices in Canine Appendicular Osteosarcoma

“…Indeed, recent evidence suggests that ALP could merely be a surrogate marker of disease burden [ 53 ] rather than a marker of aggressive biological behavior. This is supported by the similar transcriptional profiles displayed by canine OSA cell lines derived from dogs with low and high ALP [ 54 ]. Our study would then corroborate the lack of prognostic significance of ALP for dogs with similar stages, but further studies are necessary to confirm that.…”