High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy
Abstract Background Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considere...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09374-x |
| _version_ | 1819210208518340608 |
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| author | Fabio Walther Jana Ladina Berther Alexandros Lalos Michaela Ramser Simone Eichelberger Robert Mechera Savas Soysal Simone Muenst Alberto Posabella Uwe Güth Sylvia Stadlmann Luigi Terracciano Raoul A. Droeser Jasmin Zeindler Gad Singer |
| author_facet | Fabio Walther Jana Ladina Berther Alexandros Lalos Michaela Ramser Simone Eichelberger Robert Mechera Savas Soysal Simone Muenst Alberto Posabella Uwe Güth Sylvia Stadlmann Luigi Terracciano Raoul A. Droeser Jasmin Zeindler Gad Singer |
| author_sort | Fabio Walther |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS). Methods A tissue microarray of 47 primary high grade ovarian serous carcinomas and their recurrences was stained with primary antibodies directed against CXCR4 and pCXCR4. Beside the evaluation of the absolute tumor as well as TIC expression in primary and recurrent cancer biopsies the corresponding ratios for pCXCR4 and CXCR4 were generated and analyzed. The clinical endpoints were response to chemotherapy, OS as well as RFS. Results Patients with a high pCXCR4/CXCR4 TIC ratio in primary cancer biopsies showed a significant longer RFS during the first two years (p = 0.025). However, this effect was lost in the long-term analysis including a follow-up period of 5 years (p = 0.128). Interestingly, the Multivariate Cox regression analysis showed that a high pCXCR4/CXCR4 TIC ratio in primary cancer independently predicts longer RFS (HR 0.33; 95CI 0.13 - 0.81; p = 0.015). Furthermore a high dichotomized distribution of CXCR4 positive tumor expression in recurrent cancer biopsies showed a significantly longer 6-month RFS rate (p = 0.018) in comparison to patients with low CXCR4 positive tumor expression. However, this effect was not independent of known risk factors in a Multivariate Cox regression (HR 0.57; 95CI 0.24 - 1.33; p = 0.193). Conclusions To the best of our knowledge we show for the first time that a high pCXCR4/CXCR4 TIC ratio in primary HGSOC biopsies is indicative for better RFS and response to chemotherapy. Highlights • We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer. |
| first_indexed | 2024-12-23T06:07:31Z |
| format | Article |
| id | doaj.art-ef7eda99ace94779886d777c01220e5b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-23T06:07:31Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-ef7eda99ace94779886d777c01220e5b2022-12-21T17:57:33ZengBMCBMC Cancer1471-24072022-04-0122111210.1186/s12885-022-09374-xHigh ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapyFabio Walther0Jana Ladina Berther1Alexandros Lalos2Michaela Ramser3Simone Eichelberger4Robert Mechera5Savas Soysal6Simone Muenst7Alberto Posabella8Uwe Güth9Sylvia Stadlmann10Luigi Terracciano11Raoul A. Droeser12Jasmin Zeindler13Gad Singer14University Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselInstitute of Pathology, University Hospital BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselBrustzentrum ZürichInstitute of Pathology, University Hospital BaselInstitute of Pathology, University Hospital BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of BaselInstitute of Pathology, University Hospital BaselAbstract Background Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS). Methods A tissue microarray of 47 primary high grade ovarian serous carcinomas and their recurrences was stained with primary antibodies directed against CXCR4 and pCXCR4. Beside the evaluation of the absolute tumor as well as TIC expression in primary and recurrent cancer biopsies the corresponding ratios for pCXCR4 and CXCR4 were generated and analyzed. The clinical endpoints were response to chemotherapy, OS as well as RFS. Results Patients with a high pCXCR4/CXCR4 TIC ratio in primary cancer biopsies showed a significant longer RFS during the first two years (p = 0.025). However, this effect was lost in the long-term analysis including a follow-up period of 5 years (p = 0.128). Interestingly, the Multivariate Cox regression analysis showed that a high pCXCR4/CXCR4 TIC ratio in primary cancer independently predicts longer RFS (HR 0.33; 95CI 0.13 - 0.81; p = 0.015). Furthermore a high dichotomized distribution of CXCR4 positive tumor expression in recurrent cancer biopsies showed a significantly longer 6-month RFS rate (p = 0.018) in comparison to patients with low CXCR4 positive tumor expression. However, this effect was not independent of known risk factors in a Multivariate Cox regression (HR 0.57; 95CI 0.24 - 1.33; p = 0.193). Conclusions To the best of our knowledge we show for the first time that a high pCXCR4/CXCR4 TIC ratio in primary HGSOC biopsies is indicative for better RFS and response to chemotherapy. Highlights • We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer.https://doi.org/10.1186/s12885-022-09374-xOvarian cancerCXCR4PCXCR4Tumor expressionTumor infiltrating immune cellsPrognostic significance |
| spellingShingle | Fabio Walther Jana Ladina Berther Alexandros Lalos Michaela Ramser Simone Eichelberger Robert Mechera Savas Soysal Simone Muenst Alberto Posabella Uwe Güth Sylvia Stadlmann Luigi Terracciano Raoul A. Droeser Jasmin Zeindler Gad Singer High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy BMC Cancer Ovarian cancer CXCR4 PCXCR4 Tumor expression Tumor infiltrating immune cells Prognostic significance |
| title | High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy |
| title_full | High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy |
| title_fullStr | High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy |
| title_full_unstemmed | High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy |
| title_short | High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy |
| title_sort | high ratio of pcxcr4 cxcr4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy |
| topic | Ovarian cancer CXCR4 PCXCR4 Tumor expression Tumor infiltrating immune cells Prognostic significance |
| url | https://doi.org/10.1186/s12885-022-09374-x |
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