Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer
Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study eval...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/6/880 |
| _version_ | 1797722178182971392 |
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| author | Debora Basile Lorenzo Gerratana Angela Buonadonna Silvio Ken Garattini Tiziana Perin Emanuela Grassilli Gianmaria Miolo Maria Grazia Cerrito Claudio Belluco Giulio Bertola Antonino De Paoli Renato Cannizzaro Marialuisa Lavitrano Fabio Puglisi Vincenzo Canzonieri |
| author_facet | Debora Basile Lorenzo Gerratana Angela Buonadonna Silvio Ken Garattini Tiziana Perin Emanuela Grassilli Gianmaria Miolo Maria Grazia Cerrito Claudio Belluco Giulio Bertola Antonino De Paoli Renato Cannizzaro Marialuisa Lavitrano Fabio Puglisi Vincenzo Canzonieri |
| author_sort | Debora Basile |
| collection | DOAJ |
| description | Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999–2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. Results: After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; <i>p</i> = 0.005; 95% C.I. 1.75–22.79) and OS (HR: 2.54; <i>p</i> = 0.025; 95% C.I. 1.12–5.76). Conclusions: p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied. |
| first_indexed | 2024-03-12T09:44:44Z |
| format | Article |
| id | doaj.art-0c63b88d17c14e1ca6b73da6587add39 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T09:44:44Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0c63b88d17c14e1ca6b73da6587add392023-09-02T12:57:56ZengMDPI AGCancers2072-66942019-06-0111688010.3390/cancers11060880cancers11060880Role of Bruton’s Tyrosine Kinase in Stage III Colorectal CancerDebora Basile0Lorenzo Gerratana1Angela Buonadonna2Silvio Ken Garattini3Tiziana Perin4Emanuela Grassilli5Gianmaria Miolo6Maria Grazia Cerrito7Claudio Belluco8Giulio Bertola9Antonino De Paoli10Renato Cannizzaro11Marialuisa Lavitrano12Fabio Puglisi13Vincenzo Canzonieri14Department of Medicine (DAME), University of Udine, 33100 Udine, ItalyDepartment of Medicine (DAME), University of Udine, 33100 Udine, ItalyDepartment of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyDepartment of Medicine (DAME), University of Udine, 33100 Udine, ItalyPathology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, 33081 Milan, ItalyDepartment of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, 33081 Milan, ItalySurgical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalySurgical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyRadiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyDivision of Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, 33081 Milan, ItalyDepartment of Medicine (DAME), University of Udine, 33100 Udine, ItalyPathology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, ItalyBackground: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999–2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. Results: After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; <i>p</i> = 0.005; 95% C.I. 1.75–22.79) and OS (HR: 2.54; <i>p</i> = 0.025; 95% C.I. 1.12–5.76). Conclusions: p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied.https://www.mdpi.com/2072-6694/11/6/880colon cancerBruton’s tyrosine kinaseBTK |
| spellingShingle | Debora Basile Lorenzo Gerratana Angela Buonadonna Silvio Ken Garattini Tiziana Perin Emanuela Grassilli Gianmaria Miolo Maria Grazia Cerrito Claudio Belluco Giulio Bertola Antonino De Paoli Renato Cannizzaro Marialuisa Lavitrano Fabio Puglisi Vincenzo Canzonieri Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer Cancers colon cancer Bruton’s tyrosine kinase BTK |
| title | Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer |
| title_full | Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer |
| title_fullStr | Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer |
| title_full_unstemmed | Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer |
| title_short | Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer |
| title_sort | role of bruton s tyrosine kinase in stage iii colorectal cancer |
| topic | colon cancer Bruton’s tyrosine kinase BTK |
| url | https://www.mdpi.com/2072-6694/11/6/880 |
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