High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer
Abstract Background To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predict...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-11924-4 |
| _version_ | 1797274301455400960 |
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| author | Kei Furuya Masao Nakajima Ryouichi Tsunedomi Yuki Nakagami Ming Xu Hiroto Matsui Yukio Tokumitsu Yoshitaro Shindo Yusaku Watanabe Shinobu Tomochika Noriko Maeda Michihisa Iida Nobuaki Suzuki Shigeru Takeda Shoichi Hazama Tatsuya Ioka Yoshinobu Hoshii Tomio Ueno Hiroaki Nagano |
| author_facet | Kei Furuya Masao Nakajima Ryouichi Tsunedomi Yuki Nakagami Ming Xu Hiroto Matsui Yukio Tokumitsu Yoshitaro Shindo Yusaku Watanabe Shinobu Tomochika Noriko Maeda Michihisa Iida Nobuaki Suzuki Shigeru Takeda Shoichi Hazama Tatsuya Ioka Yoshinobu Hoshii Tomio Ueno Hiroaki Nagano |
| author_sort | Kei Furuya |
| collection | DOAJ |
| description | Abstract Background To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. Methods This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. Results Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175–7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. Conclusions Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC |
| first_indexed | 2024-03-07T14:56:26Z |
| format | Article |
| id | doaj.art-6147b1272ad342a6a9b324c9d9762daa |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-07T14:56:26Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6147b1272ad342a6a9b324c9d9762daa2024-03-05T19:23:58ZengBMCBMC Cancer1471-24072024-02-0124111510.1186/s12885-024-11924-4High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancerKei Furuya0Masao Nakajima1Ryouichi Tsunedomi2Yuki Nakagami3Ming Xu4Hiroto Matsui5Yukio Tokumitsu6Yoshitaro Shindo7Yusaku Watanabe8Shinobu Tomochika9Noriko Maeda10Michihisa Iida11Nobuaki Suzuki12Shigeru Takeda13Shoichi Hazama14Tatsuya Ioka15Yoshinobu Hoshii16Tomio Ueno17Hiroaki Nagano18Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineOncology Center, Yamaguchi University HospitalDepartment of Diagnostic Pathology, Yamaguchi University HospitalDepartment of Digestive Surgery, Kawasaki Medical SchoolDepartment of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of MedicineAbstract Background To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. Methods This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. Results Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175–7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. Conclusions Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRChttps://doi.org/10.1186/s12885-024-11924-4BiomarkerBevacizumabChemotherapyMetastatic colorectal cancerProteinase-3 |
| spellingShingle | Kei Furuya Masao Nakajima Ryouichi Tsunedomi Yuki Nakagami Ming Xu Hiroto Matsui Yukio Tokumitsu Yoshitaro Shindo Yusaku Watanabe Shinobu Tomochika Noriko Maeda Michihisa Iida Nobuaki Suzuki Shigeru Takeda Shoichi Hazama Tatsuya Ioka Yoshinobu Hoshii Tomio Ueno Hiroaki Nagano High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer BMC Cancer Biomarker Bevacizumab Chemotherapy Metastatic colorectal cancer Proteinase-3 |
| title | High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer |
| title_full | High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer |
| title_fullStr | High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer |
| title_full_unstemmed | High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer |
| title_short | High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer |
| title_sort | high serum proteinase 3 levels predict poor progression free survival and lower efficacy of bevacizumab in metastatic colorectal cancer |
| topic | Biomarker Bevacizumab Chemotherapy Metastatic colorectal cancer Proteinase-3 |
| url | https://doi.org/10.1186/s12885-024-11924-4 |
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