The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer
Abstract Purpose Hyaluronan modulates tumour progression, including cell adhesion, cohesion, proliferation and invasion, and the cancer stem cell phenotype. In ovarian cancer, high levels of stromal hyaluronan are associated with poor prognosis. In this work, hyaluronan synthases (HAS1-3) and hyalur...
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Springer
2022-06-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-022-04127-6 |
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| author | Jette Riecks Arianna Parnigoni Balázs Győrffy Ludwig Kiesel Alberto Passi Davide Vigetti Martin Götte |
| author_facet | Jette Riecks Arianna Parnigoni Balázs Győrffy Ludwig Kiesel Alberto Passi Davide Vigetti Martin Götte |
| author_sort | Jette Riecks |
| collection | DOAJ |
| description | Abstract Purpose Hyaluronan modulates tumour progression, including cell adhesion, cohesion, proliferation and invasion, and the cancer stem cell phenotype. In ovarian cancer, high levels of stromal hyaluronan are associated with poor prognosis. In this work, hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-4, PH-20, HYALP1) were examined with regard to different levels of gene expression and its influence on ovarian cancer patients’ survival. The impact of a siRNA depletion of HAS2 was investigated in vitro. Methods Using the Kaplan–Meier Plotter tool, we investigated the influence of hyaluronic synthases and hyaluronidases on the survival of a collective of 1435 ovarian cancer patients. Differences in gene expression between normal (n = 46) and cancerous (n = 744) ovarian tissue were examined using the TNMplot database. Following an evaluation of hyaluronan-related gene expression in the ATCC ovarian cancer panel, we studied SKOV3 and SW 626 ovarian cancer cells subjected to HAS2 siRNA or control siRNA treatment in terms of HAS1-3, HYAL2 and HYAL3 mRNA expression. We investigated the ability to form spheroids using the Hanging Drop method and the response to chemotherapy at different concentrations using the MTT Assay. By STRING analysis, interactions within the enzymes of the hyaluronic acid system and with binding partners were visualized. Results HAS1, HYAL1 and HYAL4 mRNA expression is significantly upregulated, whereas HAS2, HYAL2 and HYAL3 mRNA expression is significantly downregulated in ovarian cancer tissue compared to controls. HAS2 improves cell viability, the capability to form tumour spheroids and has a negative prognostic value regarding overall survival. Lower HAS2 expression and high expression of HYAL2 and HYAL3 favours the survival of ovarian cancer patients. HAS2 knockdown cells and control cells showed a moderate response to combinatorial in vitro chemotherapy with taxol and cisplatin. Conclusion In conclusion, our study shows that the hyaluronic acid system has a relevant influence on the survival of ovarian cancer patients and could therefore be considered as a possible prognostic factor. |
| format | Article |
| id | doaj-art-96f8aafe062d4abb8d0974ac67eced51 |
| institution | DOAJ |
| issn | 0171-5216 1432-1335 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | Springer |
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| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-96f8aafe062d4abb8d0974ac67eced512025-08-20T02:39:23ZengSpringerJournal of Cancer Research and Clinical Oncology0171-52161432-13352022-06-01148123399341910.1007/s00432-022-04127-6The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancerJette Riecks0Arianna Parnigoni1Balázs Győrffy2Ludwig Kiesel3Alberto Passi4Davide Vigetti5Martin Götte6Department of Gynecology and Obstetrics, Münster University HospitalDepartment of Gynecology and Obstetrics, Münster University HospitalDepartment of Bioinformatics, Semmelweis UniversityDepartment of Gynecology and Obstetrics, Münster University HospitalDepartment of Medicine and Surgery, University of InsubriaDepartment of Medicine and Surgery, University of InsubriaDepartment of Gynecology and Obstetrics, Münster University HospitalAbstract Purpose Hyaluronan modulates tumour progression, including cell adhesion, cohesion, proliferation and invasion, and the cancer stem cell phenotype. In ovarian cancer, high levels of stromal hyaluronan are associated with poor prognosis. In this work, hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-4, PH-20, HYALP1) were examined with regard to different levels of gene expression and its influence on ovarian cancer patients’ survival. The impact of a siRNA depletion of HAS2 was investigated in vitro. Methods Using the Kaplan–Meier Plotter tool, we investigated the influence of hyaluronic synthases and hyaluronidases on the survival of a collective of 1435 ovarian cancer patients. Differences in gene expression between normal (n = 46) and cancerous (n = 744) ovarian tissue were examined using the TNMplot database. Following an evaluation of hyaluronan-related gene expression in the ATCC ovarian cancer panel, we studied SKOV3 and SW 626 ovarian cancer cells subjected to HAS2 siRNA or control siRNA treatment in terms of HAS1-3, HYAL2 and HYAL3 mRNA expression. We investigated the ability to form spheroids using the Hanging Drop method and the response to chemotherapy at different concentrations using the MTT Assay. By STRING analysis, interactions within the enzymes of the hyaluronic acid system and with binding partners were visualized. Results HAS1, HYAL1 and HYAL4 mRNA expression is significantly upregulated, whereas HAS2, HYAL2 and HYAL3 mRNA expression is significantly downregulated in ovarian cancer tissue compared to controls. HAS2 improves cell viability, the capability to form tumour spheroids and has a negative prognostic value regarding overall survival. Lower HAS2 expression and high expression of HYAL2 and HYAL3 favours the survival of ovarian cancer patients. HAS2 knockdown cells and control cells showed a moderate response to combinatorial in vitro chemotherapy with taxol and cisplatin. Conclusion In conclusion, our study shows that the hyaluronic acid system has a relevant influence on the survival of ovarian cancer patients and could therefore be considered as a possible prognostic factor.https://doi.org/10.1007/s00432-022-04127-6Ovarian cancerHyaluronidasesHyaluronan synthasesHAS2Gene expressionSurvival analysis |
| spellingShingle | Jette Riecks Arianna Parnigoni Balázs Győrffy Ludwig Kiesel Alberto Passi Davide Vigetti Martin Götte The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer Journal of Cancer Research and Clinical Oncology Ovarian cancer Hyaluronidases Hyaluronan synthases HAS2 Gene expression Survival analysis |
| title | The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer |
| title_full | The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer |
| title_fullStr | The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer |
| title_full_unstemmed | The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer |
| title_short | The hyaluronan-related genes HAS2, HYAL1-4, PH20 and HYALP1 are associated with prognosis, cell viability and spheroid formation capacity in ovarian cancer |
| title_sort | hyaluronan related genes has2 hyal1 4 ph20 and hyalp1 are associated with prognosis cell viability and spheroid formation capacity in ovarian cancer |
| topic | Ovarian cancer Hyaluronidases Hyaluronan synthases HAS2 Gene expression Survival analysis |
| url | https://doi.org/10.1007/s00432-022-04127-6 |
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