Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy
BackgroundProgrammed death ligand 1 (PD-L1) immunohistochemistry (IHC) has been proposed as a predictive biomarker to predict response to immunotherapy. Given the limitations of IHC test in PD-L1 detection, this study aimed to investigate the technical feasibility of using quantitative RT-PCR (qRT-P...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.926746/full |
| _version_ | 1828299986470699008 |
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| author | Qingqing Qiu Jieyi Li Jieyi Li Qiaofeng Chen Xiaokai Zhao Xiaokai Zhao Ru Zhou Wenpeng Zhang Ziying Gong Ziying Gong Daoyun Zhang Daoyun Zhang Mingliang Wang Mingliang Wang |
| author_facet | Qingqing Qiu Jieyi Li Jieyi Li Qiaofeng Chen Xiaokai Zhao Xiaokai Zhao Ru Zhou Wenpeng Zhang Ziying Gong Ziying Gong Daoyun Zhang Daoyun Zhang Mingliang Wang Mingliang Wang |
| author_sort | Qingqing Qiu |
| collection | DOAJ |
| description | BackgroundProgrammed death ligand 1 (PD-L1) immunohistochemistry (IHC) has been proposed as a predictive biomarker to predict response to immunotherapy. Given the limitations of IHC test in PD-L1 detection, this study aimed to investigate the technical feasibility of using quantitative RT-PCR (qRT-PCR) to replace IHC in PD-L1 detection in gastrointestinal tumors.Materials and methodsThe Cancer Genome Atlas database was used to evaluate the relationship between PD-L1 expression in tumor tissue and the patient prognosis. In addition, 52 patients with gastrointestinal cancer were enrolled and divided into the stomach (STAD), colon (COAD), and rectum (READ) adenocarcinoma cohorts. IHC test was used to determine the PD-L1 level of the tissue specimens, and the qRT-PCR test was used to analyze the mRNA expression in both blood and tissue specimens. Moreover, the correlation between blood PD-L1 mRNA expression and immunotherapy efficacy was investigated in additional 15 patients with gastric cancer that further enrolled.ResultsThe expression level of PD-L1 in tumor tissue is related to the tumor stage of COAD (p-value = 0.001) and primary therapy outcomes in patients with READ (p-value = 0.003) but not significantly correlated to the overall survival (OS) time of patients with gastrointestinal cancer. Moreover, the concordance of PD-L1 mRNA expression level of tissue and paired blood samples is low, despite a weak linear relationship that was found in the STAD cohort (r = 0.43, p-value = 0.049). We further demonstrated that qRT-PCR results in both tissue and blood specimens were numerically but not statistically significant consistent with IHC results (corresponding to a p-value of 0.84 and 0.55, respectively). Remarkably, high PD-L1 expression in blood of patients with STAD shows a better response to immunotherapy (p-value = 0.04), which could be well identified at the relative expression cutoff of 1.5 (sensitivity of 85.7%, specificity of 75.0%, and AUC of 0.82).ConclusionsOur study established a novel strategy for rapidly distinguishing patients with gastrointestinal cancer with the response to immunotherapy and has potential clinical benefits. |
| first_indexed | 2024-04-13T13:00:42Z |
| format | Article |
| id | doaj.art-8ddb2245b4d0484ea11c0c7e34e2843c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T13:00:42Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8ddb2245b4d0484ea11c0c7e34e2843c2022-12-22T02:45:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.926746926746Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapyQingqing Qiu0Jieyi Li1Jieyi Li2Qiaofeng Chen3Xiaokai Zhao4Xiaokai Zhao5Ru Zhou6Wenpeng Zhang7Ziying Gong8Ziying Gong9Daoyun Zhang10Daoyun Zhang11Mingliang Wang12Mingliang Wang13Department of General Surgery, RuiJin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaJiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of General Surgery, RuiJin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaJiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of General Surgery, RuiJin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of General Surgery, RuiJin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaJiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing, Zhejiang, ChinaJiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing, Zhejiang, ChinaDepartment of General Surgery, RuiJin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaBackgroundProgrammed death ligand 1 (PD-L1) immunohistochemistry (IHC) has been proposed as a predictive biomarker to predict response to immunotherapy. Given the limitations of IHC test in PD-L1 detection, this study aimed to investigate the technical feasibility of using quantitative RT-PCR (qRT-PCR) to replace IHC in PD-L1 detection in gastrointestinal tumors.Materials and methodsThe Cancer Genome Atlas database was used to evaluate the relationship between PD-L1 expression in tumor tissue and the patient prognosis. In addition, 52 patients with gastrointestinal cancer were enrolled and divided into the stomach (STAD), colon (COAD), and rectum (READ) adenocarcinoma cohorts. IHC test was used to determine the PD-L1 level of the tissue specimens, and the qRT-PCR test was used to analyze the mRNA expression in both blood and tissue specimens. Moreover, the correlation between blood PD-L1 mRNA expression and immunotherapy efficacy was investigated in additional 15 patients with gastric cancer that further enrolled.ResultsThe expression level of PD-L1 in tumor tissue is related to the tumor stage of COAD (p-value = 0.001) and primary therapy outcomes in patients with READ (p-value = 0.003) but not significantly correlated to the overall survival (OS) time of patients with gastrointestinal cancer. Moreover, the concordance of PD-L1 mRNA expression level of tissue and paired blood samples is low, despite a weak linear relationship that was found in the STAD cohort (r = 0.43, p-value = 0.049). We further demonstrated that qRT-PCR results in both tissue and blood specimens were numerically but not statistically significant consistent with IHC results (corresponding to a p-value of 0.84 and 0.55, respectively). Remarkably, high PD-L1 expression in blood of patients with STAD shows a better response to immunotherapy (p-value = 0.04), which could be well identified at the relative expression cutoff of 1.5 (sensitivity of 85.7%, specificity of 75.0%, and AUC of 0.82).ConclusionsOur study established a novel strategy for rapidly distinguishing patients with gastrointestinal cancer with the response to immunotherapy and has potential clinical benefits.https://www.frontiersin.org/articles/10.3389/fonc.2022.926746/fullPD-L1IHCqRT-PCRconsistencygastrointestinal tumors |
| spellingShingle | Qingqing Qiu Jieyi Li Jieyi Li Qiaofeng Chen Xiaokai Zhao Xiaokai Zhao Ru Zhou Wenpeng Zhang Ziying Gong Ziying Gong Daoyun Zhang Daoyun Zhang Mingliang Wang Mingliang Wang Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy Frontiers in Oncology PD-L1 IHC qRT-PCR consistency gastrointestinal tumors |
| title | Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy |
| title_full | Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy |
| title_fullStr | Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy |
| title_full_unstemmed | Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy |
| title_short | Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy |
| title_sort | assessment of pd l1 mrna expression in gastrointestinal tumors and the response to immunotherapy |
| topic | PD-L1 IHC qRT-PCR consistency gastrointestinal tumors |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.926746/full |
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