Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer
Using a machine learning method, we investigated the intrinsic and extrinsic transcriptional profiles that affect the clinical response to PD-1 inhibitors in 57 patients with non-small cell lung cancer (NSCLC). Among the top 100 genes associated with the responsiveness to PD-1 inhibitors, the propor...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/1/197 |
| _version_ | 1797626140532146176 |
|---|---|
| author | Hye Eun Byeon Seokjin Haam Jae Ho Han Hyun Woo Lee Young Wha Koh |
| author_facet | Hye Eun Byeon Seokjin Haam Jae Ho Han Hyun Woo Lee Young Wha Koh |
| author_sort | Hye Eun Byeon |
| collection | DOAJ |
| description | Using a machine learning method, we investigated the intrinsic and extrinsic transcriptional profiles that affect the clinical response to PD-1 inhibitors in 57 patients with non-small cell lung cancer (NSCLC). Among the top 100 genes associated with the responsiveness to PD-1 inhibitors, the proportion of intrinsic genes in lung adenocarcinoma (LUAD) (69%) was higher than in NSCLC overall (36%) and lung squamous cell carcinoma (LUSC) (33%). The intrinsic gene signature of LUAD (mean area under the ROC curve (AUC) = 0.957 and mean accuracy = 0.9) had higher predictive power than either the intrinsic gene signature of NSCLC or LUSC or the extrinsic gene signature of NSCLC, LUAD, or LUSC. The high intrinsic gene signature group had a high overall survival rate in LUAD (<i>p =</i> 0.034). When we performed a pathway enrichment analysis, the cell cycle and cellular senescence pathways were related to the upregulation of intrinsic genes in LUAD. The intrinsic signature of LUAD also showed a positive correlation with other immune checkpoint targets, including CD274, LAG3, and PDCD1LG2 (Spearman correlation coefficient > 0.25). PD-1 inhibitor-related intrinsic gene patterns differed significantly between LUAD and LUSC and may be a particularly useful biomarker in LUAD. |
| first_indexed | 2024-03-11T10:06:15Z |
| format | Article |
| id | doaj.art-c5f0f5b340b2440f85f4604d89a9ec45 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T10:06:15Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c5f0f5b340b2440f85f4604d89a9ec452023-11-16T15:02:56ZengMDPI AGCancers2072-66942022-12-0115119710.3390/cancers15010197Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung CancerHye Eun Byeon0Seokjin Haam1Jae Ho Han2Hyun Woo Lee3Young Wha Koh4Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Hematology-Oncology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaUsing a machine learning method, we investigated the intrinsic and extrinsic transcriptional profiles that affect the clinical response to PD-1 inhibitors in 57 patients with non-small cell lung cancer (NSCLC). Among the top 100 genes associated with the responsiveness to PD-1 inhibitors, the proportion of intrinsic genes in lung adenocarcinoma (LUAD) (69%) was higher than in NSCLC overall (36%) and lung squamous cell carcinoma (LUSC) (33%). The intrinsic gene signature of LUAD (mean area under the ROC curve (AUC) = 0.957 and mean accuracy = 0.9) had higher predictive power than either the intrinsic gene signature of NSCLC or LUSC or the extrinsic gene signature of NSCLC, LUAD, or LUSC. The high intrinsic gene signature group had a high overall survival rate in LUAD (<i>p =</i> 0.034). When we performed a pathway enrichment analysis, the cell cycle and cellular senescence pathways were related to the upregulation of intrinsic genes in LUAD. The intrinsic signature of LUAD also showed a positive correlation with other immune checkpoint targets, including CD274, LAG3, and PDCD1LG2 (Spearman correlation coefficient > 0.25). PD-1 inhibitor-related intrinsic gene patterns differed significantly between LUAD and LUSC and may be a particularly useful biomarker in LUAD.https://www.mdpi.com/2072-6694/15/1/197non-small cell lung cancerPD-L1PD-1PD-1/PD-L1-targeted therapybiomarkersimmunotherapy |
| spellingShingle | Hye Eun Byeon Seokjin Haam Jae Ho Han Hyun Woo Lee Young Wha Koh Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer Cancers non-small cell lung cancer PD-L1 PD-1 PD-1/PD-L1-targeted therapy biomarkers immunotherapy |
| title | Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer |
| title_full | Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer |
| title_fullStr | Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer |
| title_full_unstemmed | Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer |
| title_short | Intrinsic and Extrinsic Transcriptional Profiles That Affect the Clinical Response to PD-1 Inhibitors in Patients with Non–Small Cell Lung Cancer |
| title_sort | intrinsic and extrinsic transcriptional profiles that affect the clinical response to pd 1 inhibitors in patients with non small cell lung cancer |
| topic | non-small cell lung cancer PD-L1 PD-1 PD-1/PD-L1-targeted therapy biomarkers immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/1/197 |
| work_keys_str_mv | AT hyeeunbyeon intrinsicandextrinsictranscriptionalprofilesthataffecttheclinicalresponsetopd1inhibitorsinpatientswithnonsmallcelllungcancer AT seokjinhaam intrinsicandextrinsictranscriptionalprofilesthataffecttheclinicalresponsetopd1inhibitorsinpatientswithnonsmallcelllungcancer AT jaehohan intrinsicandextrinsictranscriptionalprofilesthataffecttheclinicalresponsetopd1inhibitorsinpatientswithnonsmallcelllungcancer AT hyunwoolee intrinsicandextrinsictranscriptionalprofilesthataffecttheclinicalresponsetopd1inhibitorsinpatientswithnonsmallcelllungcancer AT youngwhakoh intrinsicandextrinsictranscriptionalprofilesthataffecttheclinicalresponsetopd1inhibitorsinpatientswithnonsmallcelllungcancer |