Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei
Introduction: Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC)...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000105 |
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| author | Ruiqing Ma Guojun Li Yingjiang Ye Lei Liang Chong Wang Haipeng Zhou Pu Zhang Lubiao An Guanjun Shi Qian Chen Hongbin Xu Zhidong Gao |
| author_facet | Ruiqing Ma Guojun Li Yingjiang Ye Lei Liang Chong Wang Haipeng Zhou Pu Zhang Lubiao An Guanjun Shi Qian Chen Hongbin Xu Zhidong Gao |
| author_sort | Ruiqing Ma |
| collection | DOAJ |
| description | Introduction: Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC) and dissected potential beneficial targeted therapy utilizing genomic characteristics. Methods: Whole-exome sequencing (WES) was performed on tissue specimens and matched white blood cells from 81 patients with PMP. The study investigated mutational signatures, profiling, and their correlation with progression-free survival (PFS) and overall survival (OS). Results: Signature 3 (HRD) and signature 15 (dMMR) were dominant. NMF cluster 1, characterized by signature 4, exhibited a worse prognosis. The p53 and TGF-β signaling pathways may contribute as risk factors for worse OS and PFS, respectively. MUC16-mutated patients had worse PFS (P = 0.016) and OS (P = 0.004) compared to wild-type patients. Patients with tumor mutational burden (TMB) > 1(P = 0.026) or alterations in TP53 (P = 0.006) or SMAD4 (P = 0.013) had significantly worse OS compared to those with a TMB < 1 or normal genes. Patients with homologous recombination deficiency (HRD) positivity (P = 0.003) or alterations in TGFBR2 (P = 0.037) experienced worse PFS compared to their respective control groups. Furthermore, NMF cluster1 (P = 0.020), TP53 (P = 0.004), and MUC16 (P = 0.013) were identified as independent prognostic factors for OS, while HRD status (P = 0.003) was independent predictors for PFS in PMP. Conclusions: The study reveals that genomic profiling can serve as a robust tool for identifying prognostic markers in PMP. The identified genomic mutations and signaling pathway offer new avenues for targeted therapies. |
| format | Article |
| id | doaj-art-aecd9eeaf76d44f9a90167e252cb7b01 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-aecd9eeaf76d44f9a90167e252cb7b012025-02-11T04:34:41ZengElsevierTranslational Oncology1936-52332025-03-0153102279Prognosis conferred by molecular features of appendix-derived Pseudomyxoma PeritoneiRuiqing Ma0Guojun Li1Yingjiang Ye2Lei Liang3Chong Wang4Haipeng Zhou5Pu Zhang6Lubiao An7Guanjun Shi8Qian Chen9Hongbin Xu10Zhidong Gao11Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China; Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China; Corresponding authors.Thorgene Co., Ltd., Beijing, 100176, ChinaDepartment of Gastroenterological Surgery, Peking University People's Hospital, Beijing, ChinaDepartment of Ultrasound, Aerospace Center Hospital, Beijing, China.Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, ChinaDepartment of Myxoma, Aerospace Center Hospital, Beijing, 100049, ChinaDepartment of Myxoma, Aerospace Center Hospital, Beijing, 100049, ChinaDepartment of Myxoma, Aerospace Center Hospital, Beijing, 100049, ChinaDepartment of Myxoma, Aerospace Center Hospital, Beijing, 100049, ChinaThorgene Co., Ltd., Beijing, 100176, China; Corresponding authors.Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China; Corresponding authors.Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China; Corresponding authors.Introduction: Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC) and dissected potential beneficial targeted therapy utilizing genomic characteristics. Methods: Whole-exome sequencing (WES) was performed on tissue specimens and matched white blood cells from 81 patients with PMP. The study investigated mutational signatures, profiling, and their correlation with progression-free survival (PFS) and overall survival (OS). Results: Signature 3 (HRD) and signature 15 (dMMR) were dominant. NMF cluster 1, characterized by signature 4, exhibited a worse prognosis. The p53 and TGF-β signaling pathways may contribute as risk factors for worse OS and PFS, respectively. MUC16-mutated patients had worse PFS (P = 0.016) and OS (P = 0.004) compared to wild-type patients. Patients with tumor mutational burden (TMB) > 1(P = 0.026) or alterations in TP53 (P = 0.006) or SMAD4 (P = 0.013) had significantly worse OS compared to those with a TMB < 1 or normal genes. Patients with homologous recombination deficiency (HRD) positivity (P = 0.003) or alterations in TGFBR2 (P = 0.037) experienced worse PFS compared to their respective control groups. Furthermore, NMF cluster1 (P = 0.020), TP53 (P = 0.004), and MUC16 (P = 0.013) were identified as independent prognostic factors for OS, while HRD status (P = 0.003) was independent predictors for PFS in PMP. Conclusions: The study reveals that genomic profiling can serve as a robust tool for identifying prognostic markers in PMP. The identified genomic mutations and signaling pathway offer new avenues for targeted therapies.http://www.sciencedirect.com/science/article/pii/S1936523325000105PMPGenomeMutational signaturesPrognosis |
| spellingShingle | Ruiqing Ma Guojun Li Yingjiang Ye Lei Liang Chong Wang Haipeng Zhou Pu Zhang Lubiao An Guanjun Shi Qian Chen Hongbin Xu Zhidong Gao Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei Translational Oncology PMP Genome Mutational signatures Prognosis |
| title | Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei |
| title_full | Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei |
| title_fullStr | Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei |
| title_full_unstemmed | Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei |
| title_short | Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei |
| title_sort | prognosis conferred by molecular features of appendix derived pseudomyxoma peritonei |
| topic | PMP Genome Mutational signatures Prognosis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000105 |
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