Development of renal cell carcinoma (<scp>RCC</scp>) diagnostics and impact on prognosis

Sunela, Kaisa; Lehtinen, E; Kataja, Matti; Kujala, Paula; Soimakallio, Seppo; Kellokumpu-Lehtinen, Pirkko-Liisa

doi:10.1111/bju.12242

Cited by 16 publications

(15 citation statements)

References 48 publications

(55 reference statements)

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“…Renal Cell Carcinoma (RCC) is a cancer of the renal parenchyma and the most common type of adult kidney cancer, making up 90% of renal malignancies . The incidence of RCC is increasing over recent decades, which may be related to the advanced diagnostic techniques for early detection of small renal masses and increased rates of risk factors such as obesity and hypertension . Disease stage is currently the most important factor that correlates with disease survival.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma

et al. 2016

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Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR‐194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR‐194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR‐194 expression level with multiple clinicopathological features including disease‐free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR‐194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR‐194 expression has significantly longer disease‐free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR‐194‐positive tumors retain significance in disease‐free survival and overall survival, suggesting miR‐194 is an independent marker for good prognosis in ccRCC. Moreover, miR‐194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR‐194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR‐194 is predicted to target key molecules and pathways involved in RCC progression. miR‐194 represents a prognostic biomarker in ccRCC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‐194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma

et al. 2016

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“…At present, the immunotherapy for RCC is mainly based on immune checkpoints of PD-1 and PD-L1 inhibitors [27][28][29]. However, the immunotherapy of chRCC is still insufficient.…”

Section: Discussionmentioning

confidence: 99%

Exploration of immune-related genes in high and low tumor mutation burden groups of chromophobe renal cell carcinoma

Chen

Hao³

et al. 2020

Bioscience Reports

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Renal cell carcinoma (RCC) is one of most common cancer with gradually increasing incidence and high mortality. chromogenic RCC (chRCC) is the third most common histological subtype of RCC, accounting for about 5-7% of RCC. In our study, the transcriptome expression profile data (n=89) of chRCC, corresponding clinical data (n=113) and the somatic mutation data (n=66) was obtained from the TCGA database. We first analyzed the mutation data of chRCC patients and divided chRCC patients into high and low tumor mutation burden (TMB) groups based on the median TMB. We found that high TMB was significantly associated with worse prognosis and could promote tumor metastasis and development. Moreover, four different immune-related genes (BIRC5, PDGFRL, INHBE, IL20RB) were also identified. We found that BIRC5 was significantly overexpressed in the high TMB group and correlated with worse prognosis. The result of univariate and multivariate COX analysis demonstrated that BIRC5 (HR=2.094) may serve as a prognostic indicator for patients with chRCC with high TMB. In addition, we identified the possible functional pathways of BIRC5 through GSEA enrichment. A positive correlation was obtained between BIRC5 and the abundance of CD4 + T cells. The result of our study revealed their correlation between the immune-related genes and clinicopathologic features as well as potential functional pathways as well as immune infiltrating cells, which may provide more data about the development of chRCC immunotherapy.

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“…RCC patients often have advanced disease by the time when observed due to the body is remarkably good at hiding the symptoms. Thus, improving the sensitivity of early diagnosis of tumors is helpful for reducing clinical adverse events [29]. Here, we developed a method by combined examination of gene expression levels and eQTM methylation levels to improve the performance of early diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals epithelial-mesenchymal transition-related gene FOXM1 as a novel prognostic biomarker in clear cell renal carcinoma

Jing

Song

Liu

et al. 2019

Aging

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Identification of novel clinical biomarker in clear cell renal carcinoma (ccRCC) is warranted. Integrating transcriptome (n=1669), DNA methylation (n=577) and copy number data (n=832), we developed a method to identify driver biomarkers by analyzing the omics-level dynamics of Epithelial-Mesenchymal Transition (EMT)related genes in ccRCC. We first identified 504 expression dynamic changed genes involved in ccRCC-associated key pathways such as EMT, cell cycle, EGFR and PI3K/AKT signaling. Further analysis identified 229 (90 gene promoters) aberrant expression quantitative trait methylation (eQTM) and 256 genes with expression quantitative trait copy number (eQTCN) alterations. Among them, FOXM1 was affected by both eQTM and eQTCN. FOXM1 copy number amplification (115/500, 23% of patients), occurred in an amplified peak in chromosome 12q13.3, was enriched in late-stage ccRCC samples and was associated with worse survival. FOXM1-overexpressed pT3 patients with distant metastasis showed ~25% shorter overall survival in both training (log-rank P=0.006) and validation (log-rank P=0.018) cohorts. The eQTM-gene hybrid signature (cg00044170 and FOXM1), superior to either gene expression or DNA methylation alone, showed great potential in diagnosing localized ccRCC in training (area under curve = 0.958) and validation datasets. FOXM1 could be a novel prognostic biomarker and shed light for early diagnosis at molecular level in ccRCC.

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Development of renal cell carcinoma (RCC) diagnostics and impact on prognosis

Cited by 16 publications

References 48 publications

MicroRNA‐194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma

MicroRNA‐194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma

Exploration of immune-related genes in high and low tumor mutation burden groups of chromophobe renal cell carcinoma

Multi-omics analysis reveals epithelial-mesenchymal transition-related gene FOXM1 as a novel prognostic biomarker in clear cell renal carcinoma

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