Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer
Background: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. Methods: We conducted a thorough an...
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Elsevier
2024-04-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402405432X |
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author | Hainan Yang Yanru Qiu Junjun Chen Jinzhi Lai |
author_facet | Hainan Yang Yanru Qiu Junjun Chen Jinzhi Lai |
author_sort | Hainan Yang |
collection | DOAJ |
description | Background: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. Methods: We conducted a thorough analysis of 497 UCEC samples obtained from TCGA database. Using LASSO-COX regression analysis, we constructed a radiosensitivity signature and subsequently divided patients into the radiosensitive (RS) and the radioresistant (RR) groups based on their radiosensitivity index. The GSVA and GSEA were performed to explore functional annotations. The CIBERSORT and ESTIMATE algorithms were utilized to investigate the immune infiltration status of the two groups. Additionally, we utilized the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and pRRophetic algorithms to predict the effectiveness of different treatment modalities. Results: We constructed a radiosensitivity index consists of four DNA repair-related genes. Patients in the RS group demonstrated significantly improved prognosis compared to patients in the RR group when treated with radiotherapy. We observed that the RS group exhibited a higher proportion of the POLE ultra-mutated subtype, while the RR group had a higher proportion of the copy number high subtype. GSVA enrichment analysis revealed that the RS group exhibited enrichment in DNA damage repair pathways. Notably, the RS group demonstrated a higher proportion of naïve B cells and follicular helper T cells, while regulatory T cells (Tregs) and memory B cells were more abundant in the RR group. Furthermore, patients in the RS-PD-L1-high subgroup exhibited enrichment in immune-related pathways and increased sensitivity to immunotherapy, which is likely to contribute to their improved prognosis. Additionally, we conducted in vitro experiments to validate the expression of radiosensitivity genes in non-radioresistant (AN3CA) and radioresistant (AN3CA/IR) endometrial cancer cells. Conclusions: In conclusion, our research successfully constructed a radiosensitivity signature with robust predictive capacity. These findings shed light on the association between immune activation, PD-L1 expression, and the response to immunotherapy in the context of radiotherapy. |
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issn | 2405-8440 |
language | English |
last_indexed | 2024-04-24T10:57:18Z |
publishDate | 2024-04-01 |
publisher | Elsevier |
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series | Heliyon |
spelling | doaj.art-4a486882b4314c20b65d56cd2a5c5e4a2024-04-12T04:45:35ZengElsevierHeliyon2405-84402024-04-01108e29401Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancerHainan Yang0Yanru Qiu1Junjun Chen2Jinzhi Lai3Department of Ultrasound, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, ChinaDepartment of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, ChinaNational Health Commission (NHC) Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330000, ChinaDepartment of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, China; Corresponding author.Background: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. Methods: We conducted a thorough analysis of 497 UCEC samples obtained from TCGA database. Using LASSO-COX regression analysis, we constructed a radiosensitivity signature and subsequently divided patients into the radiosensitive (RS) and the radioresistant (RR) groups based on their radiosensitivity index. The GSVA and GSEA were performed to explore functional annotations. The CIBERSORT and ESTIMATE algorithms were utilized to investigate the immune infiltration status of the two groups. Additionally, we utilized the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and pRRophetic algorithms to predict the effectiveness of different treatment modalities. Results: We constructed a radiosensitivity index consists of four DNA repair-related genes. Patients in the RS group demonstrated significantly improved prognosis compared to patients in the RR group when treated with radiotherapy. We observed that the RS group exhibited a higher proportion of the POLE ultra-mutated subtype, while the RR group had a higher proportion of the copy number high subtype. GSVA enrichment analysis revealed that the RS group exhibited enrichment in DNA damage repair pathways. Notably, the RS group demonstrated a higher proportion of naïve B cells and follicular helper T cells, while regulatory T cells (Tregs) and memory B cells were more abundant in the RR group. Furthermore, patients in the RS-PD-L1-high subgroup exhibited enrichment in immune-related pathways and increased sensitivity to immunotherapy, which is likely to contribute to their improved prognosis. Additionally, we conducted in vitro experiments to validate the expression of radiosensitivity genes in non-radioresistant (AN3CA) and radioresistant (AN3CA/IR) endometrial cancer cells. Conclusions: In conclusion, our research successfully constructed a radiosensitivity signature with robust predictive capacity. These findings shed light on the association between immune activation, PD-L1 expression, and the response to immunotherapy in the context of radiotherapy.http://www.sciencedirect.com/science/article/pii/S240584402405432XUterine corpus endometrial cancerRadiotherapyRadiosensitivityDNA repair-related genesPD-L1 |
spellingShingle | Hainan Yang Yanru Qiu Junjun Chen Jinzhi Lai Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer Heliyon Uterine corpus endometrial cancer Radiotherapy Radiosensitivity DNA repair-related genes PD-L1 |
title | Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer |
title_full | Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer |
title_fullStr | Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer |
title_full_unstemmed | Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer |
title_short | Uncovering a novel DNA repair-related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer |
title_sort | uncovering a novel dna repair related radiosensitivity model for evaluation of radiotherapy susceptibility in uterine corpus endometrial cancer |
topic | Uterine corpus endometrial cancer Radiotherapy Radiosensitivity DNA repair-related genes PD-L1 |
url | http://www.sciencedirect.com/science/article/pii/S240584402405432X |
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