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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Jing, Xiao Qin, Xiangcheng Liu, Hao Liu, Huanhuan Wang, Huina Qin, Jiayue Zhang, Yanui Cao, Shanbo Fan, Xiaodong |
| Abstract | Background DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic responses. Nonetheless, the characteristics and significance of DDR alterations in clear cell renal cell carcinoma (ccRCC) remain undefined. This study aimed to explore the predictive role, molecular mechanism, and tumor immune profile of DDR genes in ccRCC. Methods We prospectively sequenced 757 tumors and matched blood DNA samples from Chinese patients with ccRCC using next-generation sequencing (NGS) and analyzed data from 537 patients from The Cancer Genome Atlas (TCGA). A comprehensive analysis was performed. Results Fifty-two percent of Chinese patients with ccRCC harbored DDR gene mutations and 57% of TCGA patients. The immunotherapy treatment prognosis of patients with DDR gene mutations was superior to that of patients without DDR gene mutations (p = 0.047). DDR gene mutations were associated with more gene mutations and a higher tumor mutation load (TMB, p < 0.001). Moreover, patients with DDR gene mutations have a distinct mutational signature compared with those with wild-type DDR. Furthermore, the DDR-mut group had elevated neoantigen load (including single-nucleotide variants (SNV) and indel neoantigen load, p = 0.037 and p = 0.002, respectively), TCR Shannon (p = 0.025), and neutrophils (p = 0.010). DDR gene mutations exhibited a distinct immune profile with significantly higher expression levels of TNFSF9, CD70, ICAM1, and indoleamine-2,3-dioxygenase (IDO) and lower expression levels of VTCN1 and IL12A. Conclusions Our data suggest that the detection of somatic mutations in DDR genes can predict the efficacy of immunotherapy in patients with ccRCC. Furthermore, we revealed the unique molecular and immune mechanisms underlying ccRCC with DDR gene mutations. |
| Related Links | https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-024-01678-x.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s40001-024-01678-x |
| Journal | European Journal of Medical Research |
| Issue Number | 1 |
| Volume Number | 29 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-02-07 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Clear cell renal cell carcinoma (ccRCC) DNA damage repair (DDR) Prognosis Tumor microenvironment Tumor mutational burden (TMB) Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 2.9/2023 |
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