Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors
In NSCLC, there is a pressing need for immunotherapy predictive biomarkers. The processes underlying B-cell dysfunction, as well as their prognostic importance in NSCLC, are unknown. Tumor-specific B-cell gene co-expression networks were constructed by comparing the Boolean implication modeling of s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/13/3123 |
| _version_ | 1797480667593834496 |
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| author | Qing Ye Nancy Lan Guo |
| author_facet | Qing Ye Nancy Lan Guo |
| author_sort | Qing Ye |
| collection | DOAJ |
| description | In NSCLC, there is a pressing need for immunotherapy predictive biomarkers. The processes underlying B-cell dysfunction, as well as their prognostic importance in NSCLC, are unknown. Tumor-specific B-cell gene co-expression networks were constructed by comparing the Boolean implication modeling of single-cell RNA sequencing of NSCLC tumor B cells and normal B cells. Proliferation genes were selected from the networks using in vitro CRISPR-Cas9/RNA interfering (RNAi) screening data in more than 92 human NSCLC epithelial cell lines. The prognostic and predictive evaluation was performed using public NSCLC transcriptome and proteome profiles. A B cell proliferation and prognostic gene co-expression network was present only in normal lung B cells and missing in NSCLC tumor B cells. A nine-gene signature was identified from this B cell network that provided accurate prognostic stratification using bulk NSCLC tumor transcriptome (<i>n</i> = 1313) and proteome profiles (<i>n</i> = 103). Multiple genes (<i>HLA-DRA</i>, <i>HLA-DRB1</i>, <i>OAS1</i>, and <i>CD74</i>) differentially expressed in NSCLC B cells, peripheral blood lymphocytes, and tumor T cells had concordant prognostic indications at the mRNA and protein expression levels. The selected genes were associated with drug sensitivity/resistance to 10 commonly used NSCLC therapeutic regimens. Lestaurtinib was discovered as a potential repositioning drug for treating NSCLC. |
| first_indexed | 2024-03-09T22:03:22Z |
| format | Article |
| id | doaj.art-41944a63f27448a6891b65474ae514b1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:03:22Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-41944a63f27448a6891b65474ae514b12023-11-23T19:44:50ZengMDPI AGCancers2072-66942022-06-011413312310.3390/cancers14133123Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk TumorsQing Ye0Nancy Lan Guo1Lane Department of Computer Science and Electrical Engineering, Statler College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV 26506, USAWest Virginia University Cancer Institute, Morgantown, WV 26506, USAIn NSCLC, there is a pressing need for immunotherapy predictive biomarkers. The processes underlying B-cell dysfunction, as well as their prognostic importance in NSCLC, are unknown. Tumor-specific B-cell gene co-expression networks were constructed by comparing the Boolean implication modeling of single-cell RNA sequencing of NSCLC tumor B cells and normal B cells. Proliferation genes were selected from the networks using in vitro CRISPR-Cas9/RNA interfering (RNAi) screening data in more than 92 human NSCLC epithelial cell lines. The prognostic and predictive evaluation was performed using public NSCLC transcriptome and proteome profiles. A B cell proliferation and prognostic gene co-expression network was present only in normal lung B cells and missing in NSCLC tumor B cells. A nine-gene signature was identified from this B cell network that provided accurate prognostic stratification using bulk NSCLC tumor transcriptome (<i>n</i> = 1313) and proteome profiles (<i>n</i> = 103). Multiple genes (<i>HLA-DRA</i>, <i>HLA-DRB1</i>, <i>OAS1</i>, and <i>CD74</i>) differentially expressed in NSCLC B cells, peripheral blood lymphocytes, and tumor T cells had concordant prognostic indications at the mRNA and protein expression levels. The selected genes were associated with drug sensitivity/resistance to 10 commonly used NSCLC therapeutic regimens. Lestaurtinib was discovered as a potential repositioning drug for treating NSCLC.https://www.mdpi.com/2072-6694/14/13/3123B cellsT cellssingle-cell RNA sequencingCRISPR-Cas9/RNAi screeningprognostic and predictive biomarkersnon-small cell lung cancer |
| spellingShingle | Qing Ye Nancy Lan Guo Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors Cancers B cells T cells single-cell RNA sequencing CRISPR-Cas9/RNAi screening prognostic and predictive biomarkers non-small cell lung cancer |
| title | Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors |
| title_full | Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors |
| title_fullStr | Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors |
| title_full_unstemmed | Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors |
| title_short | Single B Cell Gene Co-Expression Networks Implicated in Prognosis, Proliferation, and Therapeutic Responses in Non-Small Cell Lung Cancer Bulk Tumors |
| title_sort | single b cell gene co expression networks implicated in prognosis proliferation and therapeutic responses in non small cell lung cancer bulk tumors |
| topic | B cells T cells single-cell RNA sequencing CRISPR-Cas9/RNAi screening prognostic and predictive biomarkers non-small cell lung cancer |
| url | https://www.mdpi.com/2072-6694/14/13/3123 |
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