Genomic Meta-analysis of Clear-cell Renal Cell Carcinoma (ccRCC): Aggregating Tumors to Resolve the Complexity of ccRCC

Gessner, Kathryn H.; Kim, William Y.; Zambrano, Ibardo

doi:10.1016/j.eururo.2022.01.003

Cited by 2 publications

(3 citation statements)

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“…Obesity and smoking are both risk factors for KIRC, and they are associated with oxidative stress, which suggests their involvement in the development and maintenance of KIRC ( 2 ). Surgical resection is the preferred treatment for localized KIRC, but early diagnosis is rare, and the neoplasia often presents late in the disease process or with metastasis already occurring ( 3 ). Systemic therapies are available for more advanced stages of KIRC, including cytokine therapy or tyrosine kinase inhibitors combined with immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration

et al. 2023

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Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT’s predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration

et al. 2023

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“…The proportion of genes with ctDNA in pT1a ccRCC differed from that in M1 ccRCC. The most frequently mutated gene in ccRCC is VHL , followed by PBRM1 , SETD2 , BAP1 , and KDM5C [ 19 , 27 , 28 ]. Although the proportion of genes in M1 ccRCC correlated with well-established mutational profiles, only one mutation was detected in VHL in pT1a ccRCC.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, TP53 mutations are recognized as one of the drivers of ccRCC and have also been observed in subclonal events of ccRCC [ 27 ]. A genomic meta-analysis of ccRCC demonstrated that TP53 mutations were more prevalent at metastatic sites [ 28 ]. Additionally, several ctDNA studies have shown that TP53 is one of the most frequent ctDNA-related genes in metastatic RCC [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study

Kim

Park

Choi³

et al. 2023

Cancers

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Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC.

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Genomic Meta-analysis of Clear-cell Renal Cell Carcinoma (ccRCC): Aggregating Tumors to Resolve the Complexity of ccRCC

Cited by 2 publications

References 10 publications

Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration

Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration

Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study

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