A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, generating an enormous economic and social impact that has not stopped growing in recent years. Cancer treatment for this neoplasm usually includes surgery, chemotherapy, molecular targeted treatments, and ionizing ra...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/9/2054 |
| _version_ | 1797505441379385344 |
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| author | Javier Peinado-Serrano Álvaro Quintanal-Villalonga Sandra Muñoz-Galvan Eva M. Verdugo-Sivianes Juan C. Mateos María J. Ortiz-Gordillo Amancio Carnero |
| author_facet | Javier Peinado-Serrano Álvaro Quintanal-Villalonga Sandra Muñoz-Galvan Eva M. Verdugo-Sivianes Juan C. Mateos María J. Ortiz-Gordillo Amancio Carnero |
| author_sort | Javier Peinado-Serrano |
| collection | DOAJ |
| description | Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, generating an enormous economic and social impact that has not stopped growing in recent years. Cancer treatment for this neoplasm usually includes surgery, chemotherapy, molecular targeted treatments, and ionizing radiation. The prognosis in terms of overall survival (OS) and the disparate therapeutic responses among patients can be explained, to a great extent, by the existence of widely heterogeneous molecular profiles. The main objective of this study was to identify prognostic and predictive gene signatures of response to cancer treatment involving radiotherapy, which could help in making therapeutic decisions in patients with NSCLC. To achieve this, we took as a reference the differential gene expression pattern among commercial cell lines, differentiated by their response profile to ionizing radiation (radiosensitive versus radioresistant lines), and extrapolated these results to a cohort of 107 patients with NSCLC who had received radiotherapy (among other therapies). We obtained a six-gene signature (<i>APOBEC3B</i>, <i>GOLM1</i>, <i>FAM117A</i>, <i>KCNQ1OT1</i>, <i>PCDHB2</i>, and <i>USP43</i>) with the ability to predict overall survival and progression-free survival (PFS), which could translate into a prediction of the response to the cancer treatment received. Patients who had an unfavorable prognostic signature had a median OS of 24.13 months versus 71.47 months for those with a favorable signature, and the median PFS was 12.65 months versus 47.11 months, respectively. We also carried out a univariate analysis of multiple clinical and pathological variables and a bivariate analysis by Cox regression without any factors that substantially modified the HR value of the proposed gene signature. |
| first_indexed | 2024-03-10T04:18:38Z |
| format | Article |
| id | doaj.art-142bcd21e7504a1087e5a202fb73d4a4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:18:38Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-142bcd21e7504a1087e5a202fb73d4a42023-11-23T07:54:11ZengMDPI AGCancers2072-66942022-04-01149205410.3390/cancers14092054A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung CancerJavier Peinado-Serrano0Álvaro Quintanal-Villalonga1Sandra Muñoz-Galvan2Eva M. Verdugo-Sivianes3Juan C. Mateos4María J. Ortiz-Gordillo5Amancio Carnero6Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, SpainMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, SpainInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, SpainRadiation Physics Department, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, SpainDepartment of Radiation Oncology, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, SpainInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Manuel Siurot s/n, 41013 Seville, SpainNon-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, generating an enormous economic and social impact that has not stopped growing in recent years. Cancer treatment for this neoplasm usually includes surgery, chemotherapy, molecular targeted treatments, and ionizing radiation. The prognosis in terms of overall survival (OS) and the disparate therapeutic responses among patients can be explained, to a great extent, by the existence of widely heterogeneous molecular profiles. The main objective of this study was to identify prognostic and predictive gene signatures of response to cancer treatment involving radiotherapy, which could help in making therapeutic decisions in patients with NSCLC. To achieve this, we took as a reference the differential gene expression pattern among commercial cell lines, differentiated by their response profile to ionizing radiation (radiosensitive versus radioresistant lines), and extrapolated these results to a cohort of 107 patients with NSCLC who had received radiotherapy (among other therapies). We obtained a six-gene signature (<i>APOBEC3B</i>, <i>GOLM1</i>, <i>FAM117A</i>, <i>KCNQ1OT1</i>, <i>PCDHB2</i>, and <i>USP43</i>) with the ability to predict overall survival and progression-free survival (PFS), which could translate into a prediction of the response to the cancer treatment received. Patients who had an unfavorable prognostic signature had a median OS of 24.13 months versus 71.47 months for those with a favorable signature, and the median PFS was 12.65 months versus 47.11 months, respectively. We also carried out a univariate analysis of multiple clinical and pathological variables and a bivariate analysis by Cox regression without any factors that substantially modified the HR value of the proposed gene signature.https://www.mdpi.com/2072-6694/14/9/2054NSCLCbiomarkersradiation oncologyprognosispredictive signature |
| spellingShingle | Javier Peinado-Serrano Álvaro Quintanal-Villalonga Sandra Muñoz-Galvan Eva M. Verdugo-Sivianes Juan C. Mateos María J. Ortiz-Gordillo Amancio Carnero A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer Cancers NSCLC biomarkers radiation oncology prognosis predictive signature |
| title | A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer |
| title_full | A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer |
| title_fullStr | A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer |
| title_full_unstemmed | A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer |
| title_short | A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer |
| title_sort | six gene prognostic and predictive radiotherapy based signature for early and locally advanced stages in non small cell lung cancer |
| topic | NSCLC biomarkers radiation oncology prognosis predictive signature |
| url | https://www.mdpi.com/2072-6694/14/9/2054 |
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