Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma
In metastatic renal cell carcinoma (mRCC), the clinical response to immune checkpoint inhibitors (ICIs) is limited in a subset of patients and the need exists to identify non-invasive, blood-based, predictive biomarkers for responses. We performed RNA sequencing using whole-blood samples prospective...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6207 |
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| author | Yoshiyuki Nagumo Shuya Kandori Takahiro Kojima Kazuki Hamada Satoshi Nitta Ichiro Chihara Masanobu Shiga Hiromitsu Negoro Bryan J. Mathis Hiroyuki Nishiyama |
| author_facet | Yoshiyuki Nagumo Shuya Kandori Takahiro Kojima Kazuki Hamada Satoshi Nitta Ichiro Chihara Masanobu Shiga Hiromitsu Negoro Bryan J. Mathis Hiroyuki Nishiyama |
| author_sort | Yoshiyuki Nagumo |
| collection | DOAJ |
| description | In metastatic renal cell carcinoma (mRCC), the clinical response to immune checkpoint inhibitors (ICIs) is limited in a subset of patients and the need exists to identify non-invasive, blood-based, predictive biomarkers for responses. We performed RNA sequencing using whole-blood samples prospectively collected from 49 patients with mRCC prior to the administration of ipilimumab (IPI) and/or nivolumab (NIVO) to determine whether gene expression profiles were associated with responses. An analysis from 33 mRCC patients with complete responses (<i>n</i> = 5), partial responses (<i>n</i> = 14), and progressive disease (<i>n</i> = 14) showed 460 differentially expressed genes (DEGs) related to immune responses between the responder and non-responder groups with significant differences. A set of 14 genes generated from the initial 460 DEGs accurately classified responders (sensitivity 94.7% and specificity 50.0%) while consensus clustering defined clusters with significantly differing response rates (92.3% and 35.0%). These clustering results were replicated in a cohort featuring 16 additional SD patients (49 total patients): response rates were 95.8% and 48.0%. Collectively, whole-blood gene expression profiles derived from mRCC patients treated with ICIs clearly differed by response and hierarchical clustering using immune response DEGs accurately classified responder patients. These results suggest that such screening may serve as a predictor for ICI responses in mRCC patients. |
| first_indexed | 2024-03-09T17:14:20Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:14:20Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6139770bc60448558121ae5640dbea6b2023-11-24T13:48:03ZengMDPI AGCancers2072-66942022-12-011424620710.3390/cancers14246207Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell CarcinomaYoshiyuki Nagumo0Shuya Kandori1Takahiro Kojima2Kazuki Hamada3Satoshi Nitta4Ichiro Chihara5Masanobu Shiga6Hiromitsu Negoro7Bryan J. Mathis8Hiroyuki Nishiyama9Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanDepartment of Urology, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanInternational Medical Center, University of Tsukuba Affiliated Hospital, Ibaraki 305-8576, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, JapanIn metastatic renal cell carcinoma (mRCC), the clinical response to immune checkpoint inhibitors (ICIs) is limited in a subset of patients and the need exists to identify non-invasive, blood-based, predictive biomarkers for responses. We performed RNA sequencing using whole-blood samples prospectively collected from 49 patients with mRCC prior to the administration of ipilimumab (IPI) and/or nivolumab (NIVO) to determine whether gene expression profiles were associated with responses. An analysis from 33 mRCC patients with complete responses (<i>n</i> = 5), partial responses (<i>n</i> = 14), and progressive disease (<i>n</i> = 14) showed 460 differentially expressed genes (DEGs) related to immune responses between the responder and non-responder groups with significant differences. A set of 14 genes generated from the initial 460 DEGs accurately classified responders (sensitivity 94.7% and specificity 50.0%) while consensus clustering defined clusters with significantly differing response rates (92.3% and 35.0%). These clustering results were replicated in a cohort featuring 16 additional SD patients (49 total patients): response rates were 95.8% and 48.0%. Collectively, whole-blood gene expression profiles derived from mRCC patients treated with ICIs clearly differed by response and hierarchical clustering using immune response DEGs accurately classified responder patients. These results suggest that such screening may serve as a predictor for ICI responses in mRCC patients.https://www.mdpi.com/2072-6694/14/24/6207whole-bloodgene expressionrenal cell carcinomaimmune checkpoint inhibitorresponse |
| spellingShingle | Yoshiyuki Nagumo Shuya Kandori Takahiro Kojima Kazuki Hamada Satoshi Nitta Ichiro Chihara Masanobu Shiga Hiromitsu Negoro Bryan J. Mathis Hiroyuki Nishiyama Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma Cancers whole-blood gene expression renal cell carcinoma immune checkpoint inhibitor response |
| title | Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma |
| title_full | Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma |
| title_fullStr | Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma |
| title_full_unstemmed | Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma |
| title_short | Whole-Blood Gene Expression Profiles Correlate with Response to Immune Checkpoint Inhibitors in Patients with Metastatic Renal Cell Carcinoma |
| title_sort | whole blood gene expression profiles correlate with response to immune checkpoint inhibitors in patients with metastatic renal cell carcinoma |
| topic | whole-blood gene expression renal cell carcinoma immune checkpoint inhibitor response |
| url | https://www.mdpi.com/2072-6694/14/24/6207 |
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