Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression
Abstract Backround Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T‐ and B‐cell levels change during carcinogenesis and whether such changes influence disease progression. Methods The study used a retrospective sample of 73 pro...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-03-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.7118 |
| _version_ | 1827111572121583616 |
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| author | Sudha M. Sadasivan Ian M. Loveless Yalei Chen Nilesh S. Gupta Ryan Sanii Kevin R. Bobbitt Dhananjay A. Chitale Sean R. Williamson Andrew G. Rundle Benjamin A. Rybicki |
| author_facet | Sudha M. Sadasivan Ian M. Loveless Yalei Chen Nilesh S. Gupta Ryan Sanii Kevin R. Bobbitt Dhananjay A. Chitale Sean R. Williamson Andrew G. Rundle Benjamin A. Rybicki |
| author_sort | Sudha M. Sadasivan |
| collection | DOAJ |
| description | Abstract Backround Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T‐ and B‐cell levels change during carcinogenesis and whether such changes influence disease progression. Methods The study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre‐ and post‐diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions—benign biopsy glands (BBG), tumor‐adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions—were identified using Time‐series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region‐specific lymphocyte counts and regional trends. Results The risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG‐TAG‐MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance. Conclusions Longitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course. |
| first_indexed | 2024-04-24T18:44:10Z |
| format | Article |
| id | doaj.art-62b52ef9a2a448769e4ab19d4511d716 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2025-03-20T11:16:19Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-62b52ef9a2a448769e4ab19d4511d7162024-09-19T05:15:54ZengWileyCancer Medicine2045-76342024-03-01136n/an/a10.1002/cam4.7118Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progressionSudha M. Sadasivan0Ian M. Loveless1Yalei Chen2Nilesh S. Gupta3Ryan Sanii4Kevin R. Bobbitt5Dhananjay A. Chitale6Sean R. Williamson7Andrew G. Rundle8Benjamin A. Rybicki9Department of Public Health Sciences Henry Ford Hospital Henry Ford Health + Michigan State University Health Sciences Detroit Michigan USADepartment of Public Health Sciences Henry Ford Hospital Henry Ford Health + Michigan State University Health Sciences Detroit Michigan USADepartment of Public Health Sciences Henry Ford Hospital Henry Ford Health + Michigan State University Health Sciences Detroit Michigan USADepartment of Pathology Henry Ford Hospital Detroit Michigan USADepartment of Public Health Sciences Henry Ford Hospital Henry Ford Health + Michigan State University Health Sciences Detroit Michigan USADepartment of Public Health Sciences Henry Ford Hospital Henry Ford Health + Michigan State University Health Sciences Detroit Michigan USADepartment of Pathology Henry Ford Hospital Detroit Michigan USADepartment of Pathology Cleveland Clinic Cleveland Ohio USADepartment of Epidemiology, Mailman School of Public Health Columbia University New York New York USADepartment of Public Health Sciences Henry Ford Hospital Henry Ford Health + Michigan State University Health Sciences Detroit Michigan USAAbstract Backround Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T‐ and B‐cell levels change during carcinogenesis and whether such changes influence disease progression. Methods The study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre‐ and post‐diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions—benign biopsy glands (BBG), tumor‐adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions—were identified using Time‐series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region‐specific lymphocyte counts and regional trends. Results The risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG‐TAG‐MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance. Conclusions Longitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course.https://doi.org/10.1002/cam4.7118benign biopsybiochemical recurrenceCD20CD3CD4inflammation |
| spellingShingle | Sudha M. Sadasivan Ian M. Loveless Yalei Chen Nilesh S. Gupta Ryan Sanii Kevin R. Bobbitt Dhananjay A. Chitale Sean R. Williamson Andrew G. Rundle Benjamin A. Rybicki Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression Cancer Medicine benign biopsy biochemical recurrence CD20 CD3 CD4 inflammation |
| title | Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression |
| title_full | Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression |
| title_fullStr | Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression |
| title_full_unstemmed | Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression |
| title_short | Patterns of B‐cell lymphocyte expression changes in pre‐ and post‐malignant prostate tissue are associated with prostate cancer progression |
| title_sort | patterns of b cell lymphocyte expression changes in pre and post malignant prostate tissue are associated with prostate cancer progression |
| topic | benign biopsy biochemical recurrence CD20 CD3 CD4 inflammation |
| url | https://doi.org/10.1002/cam4.7118 |
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