Dataset Information

A new risk-scoring system to predict Xp11.2 translocation renal cell carcinoma in adults.

ABSTRACT:

Objective

The objective was to derive and validate a practical scoring system for preoperative diagnosis of Xp11.2 translocation renal cell carcinoma (RCC) in adults.

Methods

Epidemiology, symptomatology, and imaging methods were correlated between patients with common RCC and those with Xp11.2 translocation RCC using a derivation study (N = 6352) and a validation study (N = 127). Univariate analysis of risk factors was performed to derive a scoring system to predict the occurrence of Xp11.2 translocation RCC in adults. The Hosmer-Lemeshow goodness-of-fit test and receiver operating characteristic (ROC) curve were used to validate the scoring system.

Results

Based on odd ratios, three low-risk factors (sex, gross haematuria, and intratumoural calcification) and three high-risk factors (age, unenhanced computed tomography density, and enhancement pattern) were given weighted scores of 1 and 2, respectively. Patients who scored 3 to 5 points underwent an additional magnetic resonance imaging examination. The final scoring system had a sensitivity of 81.0% and a specificity of 98.0%.

Conclusion

We established a practical scoring system for the preoperative diagnosis of Xp11.2 translocation RCC in adults, which can be optimised through further clinical findings in the future.

SUBMITTER: Shi Q

PROVIDER: S-EPMC7995454 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundXp11.2 translocation renal cell carcinoma (tRCC) is defined by translocation of the transcription factor E3 (TFE3) gene located on chromosome Xp11.2. Due to the high incidence in women, 17β-estradiol (E2) may be a factor influencing TFE3 breaks, and the topoisomerase II (TOP2) poison is considered one of the important risk factors in mediating DNA breaks. In this study, we investigated the potential pathogenesis of Xp11.2 tRCC using the renal epithelial cell line HK-2.MethodsImmunofluorescence assay was performed to analyze DNA breaks by quantifying phosphorylation of H2AX (γH2AX), and the micronuclei (MN) assay was designed for monitoring chromosome breaks. The chromatin immunoprecipitation (CHIP) was used to detect whether proteins bound to specific DNA site, and the co-immunoprecipitation (Co-IP) was used to confirm whether proteins bound to other proteins. In some experiments, siRNA and shRNA were transfected to knockdown target genes.ResultsOur results demonstrated that DNA double-strand breaks were mediated by TOP2β in HK-2 cells, and this process could be amplified through estrogen receptor α (ERα)-dependent pathway induced by E2. After performing translocation site analysis using target region sequencing data in two Xp11.2 tRCC cell lines and ten Xp11.2 tRCC patients, we confirmed that TOP2β and ERα could both bind to TFE3 translocation sites directly to mediate DNA breaks in a E2-dependent manner. However, TOP2β and ERα were not observed to have direct interaction, indicating that their collaborative may be implemented in other ways. Besides, TFE3 was found to be upregulated through NRF1 with increasing E2 concentration, which could increase the risk of TFE3 breaks.ConclusionOur results indicate that E2 amplifies TOP2β-mediated TFE3 breaks by ERα-dependent pathway, and E2 upregulates TFE3 by NRF1 to increase the risk of TFE3 breaks. This suggests that E2 is an important pathogenic factor for Xp11.2 tRCC pathogenesis. Video Abstract.