Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide
Abstract Background Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Method Retrospectiv...
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BMC
2024-11-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-13117-5 |
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| _version_ | 1846171862321594368 |
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| author | Heli Gao Wuhu Zhang Zheng Li Wensheng Liu Mengqi Liu Qifeng Zhuo Yihua Shi Wenyan Xu Chenjie Zhou Yi Qin Jin Xu Jie Chen Xianjun Yu Xiaowu Xu Shunrong Ji |
| author_facet | Heli Gao Wuhu Zhang Zheng Li Wensheng Liu Mengqi Liu Qifeng Zhuo Yihua Shi Wenyan Xu Chenjie Zhou Yi Qin Jin Xu Jie Chen Xianjun Yu Xiaowu Xu Shunrong Ji |
| author_sort | Heli Gao |
| collection | DOAJ |
| description | Abstract Background Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Method Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. Results In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001). Conclusion Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem. |
| format | Article |
| id | doaj-art-07be9ba86f7a4a8dbe7f208d56ee4cc4 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-07be9ba86f7a4a8dbe7f208d56ee4cc42024-11-10T12:29:51ZengBMCBMC Cancer1471-24072024-11-0124111010.1186/s12885-024-13117-5Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomideHeli Gao0Wuhu Zhang1Zheng Li2Wensheng Liu3Mengqi Liu4Qifeng Zhuo5Yihua Shi6Wenyan Xu7Chenjie Zhou8Yi Qin9Jin Xu10Jie Chen11Xianjun Yu12Xiaowu Xu13Shunrong Ji14Department of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterCenter for Neuroendocrine Tumors, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer CenterAbstract Background Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Method Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. Results In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001). Conclusion Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.https://doi.org/10.1186/s12885-024-13117-5Pancreatic neuroendocrine tumorKi67 indexCapecitabine/temozolomideUpgradingTumor microenvironment |
| spellingShingle | Heli Gao Wuhu Zhang Zheng Li Wensheng Liu Mengqi Liu Qifeng Zhuo Yihua Shi Wenyan Xu Chenjie Zhou Yi Qin Jin Xu Jie Chen Xianjun Yu Xiaowu Xu Shunrong Ji Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide BMC Cancer Pancreatic neuroendocrine tumor Ki67 index Capecitabine/temozolomide Upgrading Tumor microenvironment |
| title | Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide |
| title_full | Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide |
| title_fullStr | Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide |
| title_full_unstemmed | Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide |
| title_short | Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide |
| title_sort | distinctive grade based on ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide |
| topic | Pancreatic neuroendocrine tumor Ki67 index Capecitabine/temozolomide Upgrading Tumor microenvironment |
| url | https://doi.org/10.1186/s12885-024-13117-5 |
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