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Abstract Background N 6-methyladenosine (m6A) has been shown to participate in various essential biological processes by regulating the level of target genes. However, the function of m6A modification mediated by KIAA1429 [alias virus-like m6A methyltransferase-associated protein (VIRMA)] during the progression of diffuse large B-cell lymphoma (DLBCL) remains undefined. Methods The expression and clinical significance of KIAA1429 were verified by our clinical data. CRISPR/Cas9 mediated KIAA1429 deletion, and CRISPR/dCas9-VP64 for activating endogenous KIAA1429 was used to evaluate its biological function. RNA sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, luciferase activity assay, RNA stability experiments, and co-immunoprecipitation were performed to investigate the regulatory mechanism of KIAA1429 in DLBCL. Tumor xenograft models were established for in vivo experiments. Results Dysregulated expression of m6A regulators was observed, and a novel predictive model based on m6A score was established in DLBCL. Additionally, elevated KIAA1429 expression was associated with poor prognosis of patients with DLBCL. Knockout of KIAA1429 repressed DLBCL cell proliferation, facilitated cell cycle arrest in the G2/M phase, induced apoptosis in vitro, and inhibited tumor growth in vivo. Furthermore, carbohydrate sulfotransferase 11 (CHST11) was identified as a downstream target of KIAA1429, which mediated m6A modification of CHST11 mRNA and then recruited YTHDF2 for reducing CHST11 stability and expression. Inhibition of CHST11 diminished MOB1B expression, resulting in inactivation of Hippo–YAP signaling, reprogramming the expression of Hippo target genes. Conclusions Our results revealed a new mechanism by which the Hippo–YAP pathway in DLBCL is inactivated by KIAA1429/YTHDF2-coupled epitranscriptional repression of CHST11, highlighting the potential of KIAA1429 as a novel predictive biomarker and therapeutic target for DLBCL progression.

Abstract Despite great advance has been made in multi‐modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti‐tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune‐related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD‐L1/PD‐1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg‐modulating agents and PD‐L1/PD‐1 inhibitors.

Background: N6-methyladenosine (m6A) has been shown to participate in various essential biological processes by regulating the level of target genes. However, the function of m6A modification mediated by KIAA1429 [alias virus-like m6A methyltransferase-associated protein (VIRMA)] during the progression of diffuse large B-cell lymphoma (DLBCL) remains undefined. Methods: The expression and clinical significance of KIAA1429 were verified by our clinical data. CRISPR/Cas9 mediated KIAA1429 deletion, and CRISPR/dCas9-VP64 for activating endogenous KIAA1429 was used to evaluate its biological function. RNA sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, luciferase activity assay, RNA stability experiments, and co-immunoprecipitation were performed to investigate the regulatory mechanism of KIAA1429 in DLBCL. Tumor xenograft models were established for in vivo experiments. Results: Dysregulated expression of m6A regulators was observed, and a novel predictive model based on m6A score was established in DLBCL. Additionally, elevated KIAA1429 expression was associated with poor prognosis of patients with DLBCL. Knockout of KIAA1429 repressed DLBCL cell proliferation, facilitated cell cycle arrest in the G2/M phase, induced apoptosis in vitro, and inhibited tumor growth in vivo. Furthermore, carbohydrate sulfotransferase 11 (CHST11) was identified as a downstream target of KIAA1429, which mediated m6A modification of CHST11 mRNA and then recruited YTHDF2 for reducing CHST11 stability and expression. Inhibition of CHST11 diminished MOB1B expression, resulting in inactivation of Hippo–YAP signaling, reprogramming the expression of Hippo target genes. Conclusions: Our results revealed a new mechanism by which the Hippo–YAP pathway in DLBCL is inactivated by KIAA1429/YTHDF2-coupled epitranscriptional repression of CHST11, highlighting the potential of KIAA1429 as a novel predictive biomarker and therapeutic target for DLBCL progression. [ABSTRACT FROM AUTHOR]

Despite great advance has been made in multi‐modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti‐tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune‐related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD‐L1/PD‐1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg‐modulating agents and PD‐L1/PD‐1 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide, and its prognosis is poor. It has been reported that carbohydrate sulfotransferase 11 (CHST11) is associated with tumor progression in various cancers but rarely reported in PC. The aim of this study was to comprehensively investigate the clinical value of CHST11 in PC. Methods: CHST11 gene expression analysis was conducted by The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases. Survival analysis and receiver operating characteristic (ROC) curves were performed to evaluate the prognostic significance of CHST11 based on TCGA and International Cancer Genome Consortium (ICGC) databases. Additionally, functional enrichment analysis was also performed. Moreover, single-sample Gene Set Enrichment Analysis (ssGSEA) and ESTIMATE algorithm were used to assess immune infiltration. Finally, the relationship between CHST11 expression and immune checkpoint gene levels was estimated by Spearman's correlation analysis. Results: CHST11 was highly expressed in PC tissues compared with normal tissues, and the expression of CHST11 was related to T stage, N stage, and histological grade. The survival time of PC patients with CHST11 low-expression was significantly better than those with CHST11 high-expression. The areas under the ROC curve corresponding to 1-, 3-, and 5-year survival in the TCGA dataset were 0.573, 0.671, and 0.740, respectively, and those in the ICGC dataset were 0.588, 0.602, and 0.626, respectively. Functional enrichment analysis showed that CHST11 may be involved in the regulation of immune function. Finally, the level of CHST11 was significantly correlated with 22 types of tumor-infiltrating immune cells, immune and stromal scores, and 7 immune checkpoint genes. Conclusions: High-expression of CHST11 was correlated with poor prognosis and tumor immune infiltration in PC. Moreover, CHST11 may act as a novel prognostic marker and potential therapeutic target of PC. [ABSTRACT FROM AUTHOR]

Aberrant metabolism has been proposed as one of the emerging hallmarks of cancer. However, the interplay between metabolic disorders and cancer metastasis remains to be defined. To explore the sophisticated metabolic processes during metastatic progression, we analyzed differentially expressed metabolic genes during the epithelial-mesenchymal transition (EMT) of lung cancer cells and defined the EMT-associated metabolic gene signature in lung adenocarcinoma patients. We found that the glycosaminoglycan (GAG)-chondroitin sulfate (CS) biosynthesis pathway was upregulated in the mesenchymal state of lung cancer and associated with poor prognosis. Notably, carbohydrate sulfotransferase 11 (CHST11), a crucial CS biosynthetic enzyme, was confirmed as a poor prognosis marker in non-small cell lung cancer (NSCLC) by immunohistochemical analysis. Moreover, forced CHST11 expression promoted invasion and metastasis, which was abolished by depleting the final product of CS biosynthesis by chondroitinase ABC treatment or active-domain negative CHST11. In vivo metastasis mouse models showed that CHST11 increased lung colonies number and sulfated mucosubstance expression. Furthermore, microarray analysis revealed ceruloplasmin (CP), which facilitated iron metabolism, was the downstream effector of CHST11. CP was upregulated by CHST11 through interferon-γ signaling pathway stimulation and related to unfavorable prognosis. Both forced CP expression and long-term iron treatment increased invasion and lung colony formation. Furthermore, we found 3-AP, an iron chelator, hampered the CHST11-induced metastasis. Our findings implicate that the novel CHST11-CP-iron axis enhances EMT and may serve as a new therapeutic target to treat NSCLC patients.

Aberrant chondroitin sulfate (CS) accumulation in glioblastoma (GBM) tissue has been documented, but the role of excessive CS in GBM progression and whether it can be a druggable target are largely unknown. The aim of this study is to clarify the biological functions of CHST11 in GBM cells, and evaluate therapeutic effects of blocking CHST11-derived chondroitin 4-sulfate (C4S). We investigated the expression of CHST11 in glioma tissue by immunohistochemistry, and analyzed CHST11 associated genes using public RNA sequencing datasets. The effects of CHST11 on aggressive cell behaviors have been studied in vitro and in vivo . We demonstrated that CHST11 is frequently overexpressed in GBM tissue, promoting GBM cell mobility and modulating C4S on GBM cells. We further discovered that CSPG4 is positively correlated with CHST11, and CSPG4 involved in CHST11-mediated cell invasiveness. In addition, GBM patients with high expression of CHST11 and CSPG4 have a significantly shorter survival time. We examined the effects of treating C4S-specific binding peptide (C4Sp) as a therapeutic agent in vitro and in vivo . C4Sp treatment attenuated GBM cell invasiveness and, notably, improved survival rate of orthotopic glioma cell transplant mice. Our results propose a possible mechanism of CHST11 in regulating GBM malignancy and highlight a novel strategy for targeting aberrant chondroitin sulfate in GBM cells., Competing Interests: None., (AJCR Copyright © 2023.)

Gilles de la Tourette Sydrome (TS) is a childhood onset neurodevelopmental disorder, characterized phenotypically by the presence of multiple motor and vocal tics. It is often accompanied by multiple psychiatric comorbidities, with Attention Deficit/Hyperactivity Disorder (ADHD) among the most common. The extensive co-occurrence of the two disorders suggests a shared genetic background. A major step towards the elucidation of the genetic architecture of TS was undertaken by the first TS Genome-wide Association Study (GWAS) reporting 552 SNPs that were moderately associated with TS (p

Gilles de la Tourette Sydrome (TS) is a childhood onset neurodevelopmental disorder, characterized phenotypically by the presence of multiple motor and vocal tics. It is often accompanied by multiple psychiatric comorbidities, with Attention Deficit/Hyperactivity Disorder (ADHD) among the most common. The extensive co-occurrence of the two disorders suggests a shared genetic background. A major step toward the elucidation of the genetic architecture of TS was undertaken by the first TS Genome-wide Association Study (GWAS) reporting 552 SNPs that were moderately associated with TS (p < 1E-3). Similarly, initial ADHD GWAS attempts and meta-analysis were not able to produce genome-wide significant findings, but have provided insight to the genetic basis of the disorder. Here, we examine the common genetic background of the two neuropsychiatric phenotypes, by meta-analyzing the 552 top hits in the TSGWAS with the results of ADHD first GWASs. We identify 19 significant SNPs, with the top four implicated genes being TBC1D7, GUCY1A3, RAP1GDS1, and CHST11. TBCD17 harbors the top scoring SNP, rs1866863 (p:3.23E-07), located in a regulatory region downstream of the gene, and the third best-scoring SNP, rs2458304 (p:2.54E-06), located within an intron of the gene. Both variants were in linkage disequilibrium with eQTL rs499818, indicating a role in the expression levels of the gene. TBC1D7 is the third subunit of the TSC1/TSC2 complex, an inhibitor of the mTOR signaling pathway, with a central role in cell growth and autophagy. The top genes implicated by our study indicate a complex and intricate interplay between them, warranting further investigation into a possibly shared etiological mechanism for TS and ADHD. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OvCa) accounts for the highest tumor-related mortality among gynecological malignancies, but the underlying mechanisms are poorly understood. Glycosaminoglycans are abundantly present in ovarian tumors, and there is rising evidence that chondroitin sulfate (CS) as well as diverse carbohydrate sulfotransferases (CHSTs), the enzymes involved in the sulfation process of these structures, plays an important role in metastatic spread of tumor cells. mRNA expression levels of CHST3/7/11/12/13/15 were compared between malignant (86 OvCas) and non-malignant tumors (6 borderline tumors and 3 cystadenomas). CHST11 and CHST15 were further chosen for Western blot analysis in a cohort of 216 OvCas. Protein expression levels were correlated with clinicopathologic prognostic parameters and survival data. A significantly higher mRNA expression of CHST11, CHST12, and CHST15 was measured in ovarian cancer samples in comparison to non-malignant ones, and the same trend was observed for CHST13. For CHST3 and CHST7, no significant differences were found between the two groups. At protein level, high CHST11 expression was independently associated with unfavorable progression-free survival (PFS; p = 0.027). A similar trend was observed for CHST15, showing a nearly significant correlation between high expression levels and shorter recurrence-free survival in patients without macroscopic residual tumor after surgery ( p = 0.053). We conclude that CHSTs involved in the synthesis of CS-A and CS-E might influence ovarian cancer progression, and we suggest CHST11 as independent unfavorable prognostic factor in this entity. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans ( GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing ( WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA ( MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease. [ABSTRACT FROM AUTHOR]

In an established rat model of penetrating ballistic-like brain injury (PBBI), arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) activity was significantly reduced at the ipsilateral site of injury, but unaffected at the contralateral site or in sham controls. In addition, the ARSB substrate chondroitin 4-sulfate (C4S) and total sulfated glycosaminoglycans increased. The mRNA expression of chondroitin 4-sulfotransferase 1 (C4ST1; CHST11) and the sulfotransferase activity rose at the ipsilateral site of injury (PBBI-I), indicating contributions from both increased production and reduced degradation to the accumulation of C4S. In cultured, fetal rat astrocytes, following scratch injury, the ARSB activity declined and the nuclear hypoxia inducible factor-1α increased significantly. In contrast, sulfotransferase activity and chondroitin 4-sulfotransferase expression increased following astrocyte exposure to TGF-β1, but not following scratch. These different pathways by which C4S increased in the cell preparations were both evident in the response to injury in the PBBI-I model. Hence, findings support effects of injury because of mechanical disruption inhibiting ARSB and to chemical mediation by TGF-β1 increasing CHST11 expression and sulfotransferase activity. The increase in C4S following traumatic brain injury is because of contributions from impaired degradation and enhanced synthesis of C4S which combine in the pathogenesis of the glial scar. [ABSTRACT FROM AUTHOR]

Aberrant metabolism has been proposed as one of the emerging hallmarks of cancer. However, the interplay between metabolic disorders and cancer metastasis remains to be defined. To explore the sophisticated metabolic processes during metastatic progression, we analyzed differentially expressed metabolic genes during the epithelial-mesenchymal transition (EMT) of lung cancer cells and defined the EMT-associated metabolic gene signature in lung adenocarcinoma patients. We found that the glycosaminoglycan (GAG)-chondroitin sulfate (CS) biosynthesis pathway was upregulated in the mesenchymal state of lung cancer and associated with poor prognosis. Notably, carbohydrate sulfotransferase 11 (CHST11), a crucial CS biosynthetic enzyme, was confirmed as a poor prognosis marker in non-small cell lung cancer (NSCLC) by immunohistochemical analysis. Moreover, forced CHST11 expression promoted invasion and metastasis, which was abolished by depleting the final product of CS biosynthesis by chondroitinase ABC treatment or active-domain negative CHST11. In vivo metastasis mouse models showed that CHST11 increased lung colonies number and sulfated mucosubstance expression. Furthermore, microarray analysis revealed ceruloplasmin (CP), which facilitated iron metabolism, was the downstream effector of CHST11. CP was upregulated by CHST11 through interferon-γ signaling pathway stimulation and related to unfavorable prognosis. Both forced CP expression and long-term iron treatment increased invasion and lung colony formation. Furthermore, we found 3-AP, an iron chelator, hampered the CHST11-induced metastasis. Our findings implicate that the novel CHST11-CP-iron axis enhances EMT and may serve as a new therapeutic target to treat NSCLC patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Glycosaminoglycans (GAGs) such as heparan sulfate and chondroitin sulfate are polysaccharide chains that are attached to core proteins to form proteoglycans. The biosynthesis of GAGs is a multistep process that includes the attachment of sulfate groups to specific positions of the polysaccharide chains by sulfotransferases. Heparansulfate and heparan sulfate-sulfotransferases play important roles in growth factor signaling and animal development. However, the biological importance of chondroitin sulfation during mammalian development and growth factor signaling is poorly understood. We show that a gene trap mutation in the BMP-induced chondroitin-4-sulfotransferase 1 (C4st1) gene (also called carbohydrate sulfotransferase 11 -- Chst11), which encodes an enzyme specific for the transfer of sulfate groups to the 4-O-position in chondroitin, causes severe chondrodysplasia characterized by a disorganized cartilage growth plate as well as specific alterations in the orientation of chondrocyte columns. This phenotype is associated with a chondroitin sulfation imbalance, misiocalization of chondroitin sulfate in the growth plate and an imbalance of apoptotic signals. Analysis of several growth factor signaling pathways that are important in cartilage growth plate development showed that the C4st1gt/gt mutation led to strong upregulation of TGFβ signaling with concomitant downregulation of BMP signaling, while Indian hedgehog (Ihh) signaling was unaffected. These results show that chondroitin 4-O-sulfation by C4st1 is required for proper chondroitin sulfate localization, modulation of distinct signaling pathways and cartilage growth plate morphogenesis. Our study demonstrates an important biological role of differential chondroitin sulfation in mammalian development. [ABSTRACT FROM AUTHOR]

The t(12;14)(q23;q32) breakpoints in a case of B-cell chronic lymphocytic leukemia (B-CLL) were mapped by fluorescence in situ hybridization (FISH) and Southern blot analysis and cloned using an IGH switch-?probe. The translocation affected a productively rearranged IGH allele and the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) locus at 12q23, with a reciprocal break in intron 2 of the CHST11 gene. CHST11 belongs to the HNK1 family of Golgi-associated sulfotransferases, a group of glycosaminoglycan-modifying enzymes, and is expressed mainly in the hematopoietic lineage. Northern Blot analysis of tumor RNA using CHST11-specific probes showed expression of two CHST11 forms of abnormal size. 5'- and 3'-Rapid Amplification of cDNA Ends (RACE) revealed IGH/CHST11 as well as CHST11/IGH fusion RNAs expressed from the der(14) and der(12) chromosomes. Both fusion species contained open reading frames making possible the translation of two truncated forms of CHST11 protein. The biological consequence of t(12;14)(q23;q32) in this case presumably is a disturbance of the cellular distribution of CHST11 leading to deregulation of a chondroitin-sulfate-dependent pathway specific to the hematopoietic lineage.Oncogene (2004) 23, 6991-6996. doi:10.1038/sj.onc.1207934 Published online 26 July 2004 [ABSTRACT FROM AUTHOR]

Background: Carbohydrate sulfotransferase 11 (CHST11) is a membrane protein of Golgi that catalyses the transfer of sulfate to position 4 of the N-acetylgalactosamine residues of chondroitin. Chondroitin sulfate is the predominant proteoglycan in cartilage, and its sulfation is important in the developing growth plate of cartilage. A homozygous deletion encompassing part of the gene and the embedded miRNA MIR3922 had been detected in a woman with hand/foot malformation and malignant lymphoproliferative disease. Chst11-deficient mouse has severe chondrodysplasia, congenital arthritis and neonatal lethality. We searched for the causative variant for the unusual combination of limb malformations with variable expressivity accompanied by skeletal defects in a consanguineous Pakistani kindred., Methods: We performed detailed clinical investigations in family members. Homozygosity mapping using SNP genotype data was performed to map the disease locus and exome sequencing to identify the underlying molecular defect., Results: The limb malformations include brachydactyly, overriding digits and clino-symphalangism in hands and feet and syndactyly and hexadactyly in feet. Skeletal defects include scoliosis, dislocated patellae and fibulae and pectus excavatum. The disease locus is mapped to a 1.6 Mb region at 12q23, harbouring a homozygous in-frame deletion of 15 nucleotides in CHST11. Novel variant c.467&#95;481del (p.L156&#95;N160del) is deduced to lead to the deletion of five evolutionarily highly conserved amino acids and predicted as damaging to protein by in silico analysis. Our findings confirm the crucial role of CHST11 in skeletal morphogenesis and show that CHST11 defects have variable manifestations that include a variety of limb malformations and skeletal defects., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Ovarian cancer (OvCa) accounts for the highest tumor-related mortality among gynecological malignancies, but the underlying mechanisms are poorly understood. Glycosaminoglycans are abundantly present in ovarian tumors, and there is rising evidence that chondroitin sulfate (CS) as well as diverse carbohydrate sulfotransferases (CHSTs), the enzymes involved in the sulfation process of these structures, plays an important role in metastatic spread of tumor cells. mRNA expression levels of CHST3/7/11/12/13/15 were compared between malignant (86 OvCas) and non-malignant tumors (6 borderline tumors and 3 cystadenomas). CHST11 and CHST15 were further chosen for Western blot analysis in a cohort of 216 OvCas. Protein expression levels were correlated with clinicopathologic prognostic parameters and survival data. A significantly higher mRNA expression of CHST11, CHST12, and CHST15 was measured in ovarian cancer samples in comparison to non-malignant ones, and the same trend was observed for CHST13. For CHST3 and CHST7, no significant differences were found between the two groups. At protein level, high CHST11 expression was independently associated with unfavorable progression-free survival (PFS; p = 0.027). A similar trend was observed for CHST15, showing a nearly significant correlation between high expression levels and shorter recurrence-free survival in patients without macroscopic residual tumor after surgery (p = 0.053). We conclude that CHSTs involved in the synthesis of CS-A and CS-E might influence ovarian cancer progression, and we suggest CHST11 as independent unfavorable prognostic factor in this entity.