TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma
TP53 has been proved to be associated with cytotoxic T-cell induced apoptosis, however, the association between TP53 and the benefit of immunotherapy in melanoma has not been studied. In the present study, we examined the relationship between TP53 mutation and response to CTLA-4 blockade in metastat...
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doaj-9046837ecfe04bf48e53ae131e23e7eb2020-11-25T01:24:50ZengElsevierEBioMedicine2352-39642018-06-0132119124TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic MelanomaWenjing Xiao0Nan Du1Taoyuan Huang2Jinan Guo3Xingkui Mo4Tao Yuan5Yong Chen6Ting Ye7Chunwei Xu8Wenxian Wang9Guoqiang Wang10Shangli Cai11Jing Chen12Department of Tumor Radiotherapy, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Shinan District, Qingdao, PR ChinaDepartment of Oncology, The First Affiliated Hospital, Chinese PLA General Hospital, No. 51, Fucheng Road, Beijing, PR ChinaDepartment of Dermatologic Surgery, Dermatology Hospital of Southern Medical University, Guangdong Province Dermatology Hospital, No. 2, Lujing Road, Yuexiu District, Guangdong Province, PR ChinaThe Department of Urology, The Second Clinical Medical College of Jinan University (Shenzhen people's Hospital), Shenzhen Urology Minimally Invasive Engineering Center, Shenzhen, PR ChinaDepartment of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, No 519, Kunzhou Road, Xishan District, Kunming, Yunnan Province, PR ChinaDepartment of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, No 519, Kunzhou Road, Xishan District, Kunming, Yunnan Province, PR ChinaDepartment of musculoskeletal surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR ChinaDepartment of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, PR ChinaDepartment of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR ChinaThe Medical Department, 3D Medicines Inc., Shanghai, PR ChinaThe Medical Department, 3D Medicines Inc., Shanghai, PR ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Corresponding author.TP53 has been proved to be associated with cytotoxic T-cell induced apoptosis, however, the association between TP53 and the benefit of immunotherapy in melanoma has not been studied. In the present study, we examined the relationship between TP53 mutation and response to CTLA-4 blockade in metastatic melanoma by analyzing the data from one public cohort consisting of 110 patients with metastatic melanoma. The sequencing, mRNA and survival data of 368 patients with skin melanoma from The Cancer Genome Atlas (TCGA) was used to explore the underlying mechanism. TP53 mutation was associated with significant poorer progression-free survival (HR, 2.25; 95% CI, 1.15–4.37; P = 0.014), poorer overall survival (HR, 2.05; 95% CI, 1.02–4.13; P = 0.040) and trend of poorer response (OR, 0.20; 95% CI, 0.02–1.62; P = 0.131). The correlations were significant in multivariate analysis including lactate dehydrogenase, tumor mutational burden and tumor stage (P < 0.05). In TCGA, no association was observed between TP53 mutation and survival (P = 0.55). The mRNA expression of FAS was lower in patients with TP53 mutation than TP53 wild-type. Our findings suggest that TP53 mutation is a potential negative predictor of metastatic melanoma treated with CTLA-4 blockade. Keyword: Anti-CTLA-4, TP53, Melanoma, Biomarker, Tumor mutational burdenhttp://www.sciencedirect.com/science/article/pii/S235239641830183X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenjing Xiao Nan Du Taoyuan Huang Jinan Guo Xingkui Mo Tao Yuan Yong Chen Ting Ye Chunwei Xu Wenxian Wang Guoqiang Wang Shangli Cai Jing Chen |
spellingShingle |
Wenjing Xiao Nan Du Taoyuan Huang Jinan Guo Xingkui Mo Tao Yuan Yong Chen Ting Ye Chunwei Xu Wenxian Wang Guoqiang Wang Shangli Cai Jing Chen TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma EBioMedicine |
author_facet |
Wenjing Xiao Nan Du Taoyuan Huang Jinan Guo Xingkui Mo Tao Yuan Yong Chen Ting Ye Chunwei Xu Wenxian Wang Guoqiang Wang Shangli Cai Jing Chen |
author_sort |
Wenjing Xiao |
title |
TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma |
title_short |
TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma |
title_full |
TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma |
title_fullStr |
TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma |
title_full_unstemmed |
TP53 Mutation as Potential Negative Predictor for Response of Anti-CTLA-4 Therapy in Metastatic Melanoma |
title_sort |
tp53 mutation as potential negative predictor for response of anti-ctla-4 therapy in metastatic melanoma |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2018-06-01 |
description |
TP53 has been proved to be associated with cytotoxic T-cell induced apoptosis, however, the association between TP53 and the benefit of immunotherapy in melanoma has not been studied. In the present study, we examined the relationship between TP53 mutation and response to CTLA-4 blockade in metastatic melanoma by analyzing the data from one public cohort consisting of 110 patients with metastatic melanoma. The sequencing, mRNA and survival data of 368 patients with skin melanoma from The Cancer Genome Atlas (TCGA) was used to explore the underlying mechanism. TP53 mutation was associated with significant poorer progression-free survival (HR, 2.25; 95% CI, 1.15–4.37; P = 0.014), poorer overall survival (HR, 2.05; 95% CI, 1.02–4.13; P = 0.040) and trend of poorer response (OR, 0.20; 95% CI, 0.02–1.62; P = 0.131). The correlations were significant in multivariate analysis including lactate dehydrogenase, tumor mutational burden and tumor stage (P < 0.05). In TCGA, no association was observed between TP53 mutation and survival (P = 0.55). The mRNA expression of FAS was lower in patients with TP53 mutation than TP53 wild-type. Our findings suggest that TP53 mutation is a potential negative predictor of metastatic melanoma treated with CTLA-4 blockade. Keyword: Anti-CTLA-4, TP53, Melanoma, Biomarker, Tumor mutational burden |
url |
http://www.sciencedirect.com/science/article/pii/S235239641830183X |
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