Growth Differentiation Factor-15 as Biomarker in Uterine Sarcomas

Trovik, Jone; Salvesen, Helga B.; Cuppens, Tine; Amant, Frédéric; Staff, Anne Cathrine

doi:10.1097/igc.0000000000000037

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…GDF15 has also been reported as a nonspecific biomarker for many diseases, including cancer, cardiac, pulmonary, renal, and gynecological disease (Izumiya et al 2014;Kempf and Wollert 2013;Trovik et al 2014;Yang et al 2014). Since several of these conditions are highly prevalent in m.3243A>G carriers (de Laat et al 2012;Hirano et al 2002), including kidney failure (Breit et al 2012), diabetes mellitus (Dominguez-Rodriguez et al 2014), and cardiomyopathy (Montoro-Garcia et al 2012), the contribution of these conditions to the concentration of GDF15 was studied in more detail.…”

Section: Discussionmentioning

confidence: 99%

“…GDF15 was already known as a quite nonspecific biomarker for cancer, as well as cardiac, pulmonary, renal, and gynecological disease (Izumiya et al 2014;Kempf and Wollert 2013;Trovik et al 2014;Yang et al 2014;Breit et al 2012;Montoro-Garcia et al 2012). However, the concentrations reported in these disorders are within the 1.000-7.000 pg/ mL range (Dominguez-Rodriguez et al 2014;Ho et al 2013;Izumiya et al 2014;Montoro-Garcia et al 2012;Trovik et al 2014), whereas concentrations as high as 85.252 pg/mL were reported in patients with mitochondrial disease (Kalko et al 2014). A child with the m.3243A>G mutation, the most commonly observed mutation leading to mitochondrial disease, was reported to have a concentration of 6.999 pg/ mL (reference value, 380 pg/mL (95%CI, 59-701 pg/mL)).…”

Section: Introductionmentioning

confidence: 99%

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Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

et al. 2015

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In this observational cohort study, we examined the prognostic value of growth and differentiation factor 15 (GDF15) in indicating and monitoring general mitochondrial disease severity and progression in adult carriers of the m.3243A>G mutation.Ninety-seven adult carriers of the m.3243A>G mutation were included in this study. The Newcastle mitochondrial disease adult scale was used for rating mitochondrial disease severity. In parallel, blood was drawn for GDF15 analysis by ELISA. Forty-nine carriers were included in a follow-up study. In a small subset of subjects of whom an echocardiogram was available from general patient care, myocardial deformation was assessed using two-dimensional speckle-tracking strain analysis.A moderate positive correlation was found between the concentration of GDF15 and disease severity (r ¼ 0.59; p < 0.001). The concentration of serum GDF15 was higher in m.3243A>G carriers with diabetes mellitus, cardiomyopathy, and renal abnormalities. After a 2-year follow-up, no significant correlation was found between the change in disease severity and the change in the concentration of GDF15 or between the GDF15 level at the first assessment and the change in disease severity. In the subcohort of patients of whom an echocardiogram was available, the concentration of GDF15 correlated moderately to longitudinal global strain (r ¼ 0.55; p ¼ 0.006; n ¼ 23) but not to circumferential or radial strain.Our results indicate that serum GDF15 is not a strong surrogate marker for general mitochondrial disease severity. Its value in indicating myocardial deformation should be confirmed in a prospective longitudinal study.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

et al. 2015

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“…Significantly higher levels of GDF-15 correlated with high stage, low differentiation, non-endometrioid histopathological type, hormonal status and lymph node involvement 36. In light of studies conducted by Trovik et al37 GDF-15 appears to be a very good marker for the differentiation of benign mesenchymal tumors from uterine sarcomas. To date, only one report has been published with regard to the behavior of GDF-15 within the peritoneal fluid 39.…”

Section: Discussionmentioning

confidence: 95%

Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions

Chudecka‐Głaz

Cymbaluk‐Płoska

Menkiszak

et al. 2015

OTT

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ObjectivesThe ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer.MethodsA total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed.ResultsDifferences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients.ConclusionOn the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin.

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“…Furthermore, one retrospective study has found a significantly elevated NLR in the STS group (n=83) compared to benign soft tissue tumors (n=140) (p<0.001) (56). In addition, two studies found significantly elevated [10] UM [24] NS USC [15] UM [19] NS LDH (21)(22)(23) LMS [10] UM [15] p=0.0093 USC [15] UM [19] p=0.001 USC [15] UM [48] p<0.001 GDF-15 (60) USC [19] UM [50], healthy controls [40] p=0.007, p=0.002…”

Section: Relevance Of Immune Related Protein Biomarkers In the Diagnomentioning

confidence: 99%

“…Cho et al (2015) compared 31 women with uterine sarcomas (14 ESS, 11 LMS, 6 USS) to 93 with uterine myomas and found statistically higher preoperative NLR values in the sarcoma group (57). Trovik et al, studied 19 patients with uterine sarcomas (13 LMS, four ESS, one AS and one USS), 50 with uterine myomas and 40 healthy controls and demonstrated a significantly higher median GDF-15 plasma concentration in the sarcoma group compared to the myoma group and healthy controls (60).…”

Section: Relevance Of Immune Related Protein Biomarkers In the Diagnomentioning

confidence: 99%

Circulating Protein Biomarkers to Differentiate Uterine Sarcomas from Leiomyomas

et al. 2019

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Uterine sarcomas are rare but very aggressive. Uterine myomas, on the other hand, are the most common benign tumors of the uterus. Currently there is no diagnostic technique available to distinguish them with certainty. This study aimed to summarize the published literature concerning protein-based biomarkers in the peripheral blood that can assist in this difficult differential diagnosis. In total, 48 articles, published between 1990 and 2017, were included. Most studies (n=37) concerned soft tissue sarcomas, while 11 discussed uterine sarcomas specifically. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukins (IL), cancer antigen 125 (CA 125), lactate dehydrogenase, gangliosides (LDH) and growth differentiation factor 15 (GDF-15) are the most studied proteins in soft tissue sarcomas, including uterine sarcomas. Future research on improving sarcoma diagnosis should include these proteins.

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Growth Differentiation Factor-15 as Biomarker in Uterine Sarcomas

Cited by 25 publications

References 26 publications

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions

Circulating Protein Biomarkers to Differentiate Uterine Sarcomas from Leiomyomas

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Growth Differentiation Factor-15 as Biomarker in Uterine Sarcomas

Cited by 25 publications

References 26 publications

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

Assessment of selected cytokines, proteins, and&nbsp;growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions

Circulating Protein Biomarkers to Differentiate Uterine Sarcomas from Leiomyomas

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Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions