High Serum Levels of Follistatin in Patients with Ovarian Cancer

Ren, Pinyi; Ff, Chen; Hy, Liu; Xl, Cui; Sun, Ying‐Shi; Jl, Guan; Zh, Liu; Jg, Liu; Yn, Wang

doi:10.1177/147323001204000306

Cited by 25 publications

(25 citation statements)

References 23 publications

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“…These findings provoked studies investigating FST as a diagnostic or prognostic marker for solid tumours. One study showed that serum FST and ovarian carcinoma antigen CA125 levels were significantly increased in patients with ovarian cancer when compared with healthy individuals and patients with benign ovarian cysts, which suggests that the serum FST level has potential diagnostic value, especially when combined with CA125 detection in order to reduce the number of false-positive results (105). Serum levels of FST were also found to be elevated in patients with hepatocellular cancer (HCC) (21,106).…”

Section: Value Of Follistatin In Diagnosis Prognosis and Of Solid Tumentioning

confidence: 99%

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Shi

Resaul

Owen

et al. 2016

CGP

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Abstract. Follistatin (FST) Follistatin (FST), which was first isolated from porcine and bovine follicular fluid (1, 2), was initially described as a protein involved in the regulation of the secretion of folliclestimulating hormone. This monomeric glycosylated polypeptide chain is encoded by a single gene located on the long arm chromosome 5q11.2 (3), which through alternative splicing may be transcribed into the mRNA precursors, FST317 and FST344. From these precursors, three major FST isoforms may be produced, namely FST288 (from pre-FST317), FST315 (from pre-FST344) and a third FST isoform, FST303, produced from the post-translational truncation of the FST315 C-terminus. These three main FST isoforms can also be glycosylated to yield six further FST isoforms that were previously identified in bovine (4) and porcine (5, 6) follicular fluid. At the core, all FST isoforms contain a 63 residue N-terminal domain and three follistatin domains, termed FSD1, FSD2 and FSD3. These domains comprise 73-77 amino acid residues and are characterised by an arrangement of 10 conserved cysteine residues (7). Both FST288 and FST315 are differentially expressed in human tissues (6-9). FST315 is the predominant isoform, whilst the FST288 isoform accounts for less than 5% of the encoded mRNA (10, 11). Some molecules such as activin, transforming growth factor-beta (TGFβ), forkhead domain transcription factor L2 (12, 13), gonadotropin-releasing hormone (14), zinc finger protein (GLI2) (15), dexamethasone (16), androgens (17), activators of winglessrelated integration site (WNT) signalling (18, 19) and 1,25-dihydroxyvitamin D (20) have been shown to regulate the transcription of the FST gene. In addition, down-regulation of FST gene expression by peroxisome proliferator-activated receptor gamma (PPARγ) or the transcription factor epiprofin (21, 22) has been shown.As an antagonist of TGFβ superfamily member activin, FST seems to primarily function in relation to the role that activin plays. Along with FST, activin acts as a pleiotropic growth factor system, which is involved in proliferation, differentiation, and apoptosis of a number of cell types (23-28). As such, the functions of the FST isoforms are therefore linked to their binding affinity for activin (6,10,11,(29)(30)(31)(32)(33)(34)(35)(36)(37). In fact, this critical binding and neutralisation of activin, either partial or complete, is based on the order of at least two of the FST cysteine domains and its Nterminal (38), conferring a difference in affinities for activin between the FST isoforms. The binding complex between activin and FST generally occurs in a 1:2 ratio, where the two FST molecules, connected C-terminus to N-425

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Section: Value Of Follistatin In Diagnosis Prognosis and Of Solid Tumentioning

confidence: 99%

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Shi

Resaul

Owen

et al. 2016

CGP

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“…FST is a specific binding protein of activin and is involved in the regulation of pathophysiological functions, including early embryonic development and differentiation of ovarian granulosa cells . A recent study suggested that FST protein expression was immunohistochemically detected in 53% of ovarian cancers, and that high serum levels of FST were found in the patients . Therefore, we study histopathological features of the FOXL2 p.C134W mutation‐positive and ‐negative GCT regarding the expression of BMP2 and FST immunohistochemically.…”

Section: Introductionmentioning

confidence: 98%

Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary

Oseto

Suzumori

Nishikawa

et al. 2014

J of Obstet and Gynaecol

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Aim: To assess whether FOXL2 p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin-α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors. Methods: We analyzed 114 tumor tissues from ovarian tumors, including 44 adult-type and two juvenile-type GCT of the ovary and 68 ovarian tumors by DNA sequencing. Immunohistochemistry was also performed in the adult and juvenile GCT tissues by immunostaining inhibin-α, BMP2 and FST. Results: We found the FOXL2 p.C134W mutation in 27 out of 44 (61.4%) adult-type GCT of the ovary, but none in other ovarian tumors. Histologically, all of the adult-type GCT sections were positive for inhibin-α, and the expression of BMP2 and FST was detected in 14 of 44 (31.8%) and zero of 47 (0%), respectively. No significant differences regarding the diagnosed age, preoperative serum carbohydrate antigen 125 levels, or BMP2 immunopositivity between the FOXL2 p.C134W mutation-positive and mutation-negative were found in the adult-type GCT patients. Conclusion: Our findings suggest that FOXL2 p.C134W mutation-positive adult-type GCT of the ovary may not be common in the Japanese as compared to the previous data.

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“…FST binds activin to inhibit its activity 34) , and dysregulation of the FST and activin axis is one of the most significant factors underlying tumor genesis. FST has been reported as a biomarker or therapeutic target in cancers such as breast cancer 35) , ovarian cancer 36,37) , hepatocellular carcinoma 23) , and glioblastoma 38) . Recently, Chen et al reported that FST is a novel biomarker for the diagnosis of lung adenocarcinoma 22) .…”

Section: Discussionmentioning

confidence: 99%

Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

Qiao

Kito²,

Takai³

et al. 2017

J. Electrophor

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SUMMARYSarcoma is a rare malignancy with an aggressive clinical course. Tyrosine kinase inhibitors (TKIs) have emerged as effective drugs in targeted therapy for malignancies; in particular, pazopanib was recently approved for the treatment of sarcoma. However, as only a limited proportion of patients exhibit favorable response to treatment with TKIs, predictive biomarkers of response to these drugs are urgently needed. In this study, we attempted to identify predictive biomarkers for response to TKIs in synovial sarcoma. We performed a magnetic bead-based assay (Bio-Plex) using synovial sarcoma cell culture supernatant and validated the results by ELISA and western blotting. Cellular protein and mRNA expression levels of candidate biomarkers were evaluated by western blotting and RT-PCR. Gene expression profiling of candidate biomarkers was conducted by meta-analysis of publicly available gene expression data from 149 patients with synovial sarcoma. We found that follistatin (FST) was significantly highly expressed in TKI-resistant cells. Moreover, cell proliferation was decreased following gene silencing of FST. Meta-analysis revealed that the mRNA expression of FST varied among the 149 patients with synovial sarcoma, and that 23 genes were co-expressed with FST; these included genes encoding receptor tyrosine kinase-like orphan receptor 1, Sal-like protein 4, and signal transducer CD24. This study suggested that FST represents a candidate predictive biomarker for response to treatment with TKIs in synovial sarcoma. Secretomics is a promising approach for predictive biomarker exploration. The utility of FST as a predictive biomarker for response to treatment with TKIs in synovial sarcoma should be further validated using clinical samples.

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High Serum Levels of Follistatin in Patients with Ovarian Cancer

Abstract: The serum FST level was elevated in the peripheral blood of patients with ovarian cancer and has potential as a tumour marker for ovarian cancer diagnosis. It may be particularly useful when combined with CA-125 detection to reduce the number of false-positive results.

Cited by 25 publications

References 23 publications

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary

Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

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