Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcomas

Morgan, Sara; Nagle, Raymond B.; Cranmer, Lee D.

doi:10.1186/2045-3329-4-2

Cited by 4 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of serum protein acidic and rich in cysteine (SPARC), a biomarker for albumin bound paclitaxel, was seen in 35.9% of the cases, especially in over 60% of epithelioid hemangioendothelioma (EHE) and chondrosarcoma (notably conventional chondrosarcoma), as well as 48.7% of angiosarcomas. A previous study of SPARC expression by IHC, noted a rate of high SPARC staining in 56% of specimens, but given the small sample size ( n = 27), specific histology correlations could not be made [ 12 ]. Low MGMT expression, a temozolomide associated biomarker, was noted in a variety of sarcomas including alveolar soft part sarcoma (21 ASPS), desmoid, EHE, perivascular epithelioid cell tumor (PEComa), endometrial stromal sarcoma (ESS), giant cell tumor, liposarcoma, LMS, malignant peripheral nerve sheath tumor (MPNST), osteosarcoma and UPS.…”

Section: Resultsmentioning

confidence: 99%

“…Clinically, angiosarcomas and EHE are essentially the only sarcoma subtypes where single agent taxanes are of benefit [ 39 ]. Though, SPARC expression has been assessed in sarcoma specimens, only 1 case of angiosarcoma has previously been evaluated and was found to have high expression of SPARC [ 12 ]. In our study, interestingly, SPARC was overexpressed in angiosarcoma, chondrosarcoma and EHE.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets

et al. 2015

View full text Add to dashboard Cite

Background: Drug development in sarcoma has been hampered by the rarity and heterogeneity of the disease and lack of predictive biomarkers to therapies. We assessed protein expression and gene alterations in a large number of bone and soft tissue sarcomas in order to categorize the molecular alterations, identify predictive biomarkers and discover new therapeutic targets. Methods: Data from sarcoma specimens profiled for protein expression, gene amplification/translocation and DNA sequencing was reviewed. Results: 2539 sarcoma specimens of 22 subtypes were included. TOPO2A was the most overexpressed protein at 52.8%. There was overexpression or loss of other sarcoma relevant proteins such as SPARC, PTEN and MGMT. Approximately 50% of the sarcomas expressed PD-L1 by IHC and presented with PD-1+ TILs, notably the LMS, chondrosarcomas, liposarcomas and UPS. Gene amplification/rearrangement of ALK, cMYC, HER2, PIK3CA, TOPO2A and cMET was relatively uncommon. EGFR gene amplification occurred at a rate of 16.9%. DNA sequencing of 47 genes identified mutations in 47% of the samples. The most commonly mutated genes were TP53 (26.3%) and BRCA2 (17.6%). Overexpression of TOPO2A was associated with TP53 mutation (P = 0.0001). Conclusion: This data provides the landscape of alterations in sarcoma. Future clinical trials are needed to validate these targets.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Cyclin D1 expression is induced by mitogens and is crucial for G1 progression[33]. Previous results showed that Smoc2 plays an important role in promoting G1/S progression through participating in the maintenance of cyclin D1 expression[34-36]. In other words, cyclin D1 can be considered as an effector of Smoc2-induced DNA synthesis[37,38].…”

Section: Discussionmentioning

confidence: 99%

Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

Su¹,

Kuai²,

Li³

2016

WJG

View full text Add to dashboard Cite

AIMTo determine the influence of Smoc2 on hepatocellular carcinoma (HCC) cell proliferation and to find a possible new therapeutic target for preventing HCC progression.METHODSWe detected expression of Smoc2 in HCC tissues and corresponding non-tumor liver (CNL) tissues using PCR, western blot, and immunohistochemistry methods. Subsequently, we down-regulated and up-regulated Smoc2 expression using siRNA and lentivirus transfection assay, respectively. Then, we identified the effect of Smoc2 on cell proliferation and cell cycle using CCK-8 and flow cytometry, respectively. The common cell growth signaling influenced by Smoc2 was detected by western blot assay.RESULTSThe expression of Smoc2 was significantly higher in HCC tissues compared with CNL tissues. Overexpression of Smoc2 promoted HCC cell proliferation and cell cycle progression. Down-regulation of Smoc2 led to inhibition of cell proliferation and cell cycle progression. Smoc2 had positive effect on ERK and AKT signaling.CONCLUSIONSmoc2 promotes the proliferation of HCC cells through accelerating cell cycle progression and might act as an anti-cancer therapeutic target in the future.

show abstract

“…IHC cutoffs for SPARC have not been established in sarcoma. Previous evaluation of SPARC expression in sarcoma has defined overexpression as a staining intensity of 2+ and percentage of cells stained ranging from 30 to 50 % [ 10 , 12 ]. IHC results in our study were also assessed based upon staining intensity and percentage of cells stained.…”

Section: Methodsmentioning

confidence: 99%

“…SPARC levels did not correlate with specific histologies but did correlate with OS. Low SPARC expressers had a median survival of 22.1 months while in the high expressers, the median survival was 4.4 months [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

SPARC expression in patients with high-risk localized soft tissue sarcoma treated on a randomized phase II trial of neo/adjuvant chemotherapy

et al. 2016

View full text Add to dashboard Cite

BackgroundTreatment for localized soft tissue sarcoma includes surgery and radiation, while the role of chemotherapy is controversial. Biomarkers that could predict therapeutic response or prognosticate overall survival (OS) are needed to define patients most likely to benefit from systemic treatment. Serum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that has been evaluated as a potential biomarker in numerous malignancies given its involvement in cell adhesion, proliferation, migration, and tissue remodeling.MethodsUsing primary biopsy and resection specimens from patients with high-risk localized, soft tissue sarcoma treated on a neo/adjuvant chemotherapy study, SPARC expression was assessed and compared to patient and tumor characteristics, treatment, and outcomes. Survival functions were estimated using the Kaplan–Meier method and compared using the log-rank test. The Cox model was used for multivariate analysis.ResultsFifty patients had primary tumor specimens available. High, low, and no SPARC expression was found in 22, 13, and 15 patients, respectively. There was no significant difference in time to recurrence or OS between patients in these three groups. Comparing lack of SPARC expression with any SPARC expression, there was no significant difference in time to recurrence in patients without SPARC expression (n = 15) compared to patients with SPARC expression (n = 35). Likewise, there was no statistically significant difference in OS in patients without SPARC expression versus patients whose tumors expressed SPARC.ConclusionsAlthough we did not find a statistically significant difference in time to recurrence and OS in patients with high-risk soft tissue sarcoma, we did identify a trend toward improved time to recurrence and OS in patients whose tumors lacked SPARC expression. However, SPARC did not demonstrate the ability to discern which high-risk patients may have a worse prognosis or greater benefit from chemotherapy.Trial registrationThe trial was registered on September 13, 2005 with ClinicalTrials.gov, number https://clinicaltrials.gov/ct2/show/NCT00189137?term=sarcoma&id=NCT00189137&state1=NA%3AUS%3AMI&phase=1&rank=1.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2694-2) contains supplementary material, which is available to authorized users.

show abstract

Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcomas

Cited by 4 publications

References 25 publications

Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets

Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets

Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

SPARC expression in patients with high-risk localized soft tissue sarcoma treated on a randomized phase II trial of neo/adjuvant chemotherapy

Contact Info

Product

Resources

About