Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database

Wolff, Ingmar; May, Matthias; Hoschke, B.; Zigeuner, Richard; Cindolo, Luca; Hutterer, Georg C.; Schips, Luigi; Cobelli, Ottavio De; Rocco, Bernardo; Nunzio, Cosimo De; Tubaro, Andrea; Coman, I.; Feciche, Bogdan; Truß, Michael C.; Dalpiaz, Orietta; Figenshau, R. Sherburne; Madison, Kerry; Sánchez‐Chapado, Manuel; Martin, Maria del Carmen Santiago; Salzano, L.; Lotrecchiano, Giuseppe; Shariat, Shahrokh F.; Hohenfellner, Markus; Waidelich, Raphaela; Stief, Christian G.; Miller, Kurt; Pahernik, Sascha; Brookman‐May, Sabine

doi:10.1016/j.ejso.2016.01.009

Cited by 48 publications

(30 citation statements)

References 17 publications

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“…More than 30% of patients usually are at metastasis by the time they are diagnosed ( Cairns, 2010 ). There are about 30% of the localized ccRCC patients with curative intent who eventually have recurrence or develop metastatic disease following radical or partial nephrectomy ( Meskawi et al, 2012 ; Wolff et al, 2016 ; Hsieh et al, 2017 ). Therefore, it is essential to identify more novel prognostic signatures and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

Zhao

Khan

et al. 2020

Front. Genet.

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Background Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), which accounts for majority of RCC-related deaths. It is clearly essential to further identify more novel prognostic signatures and therapeutic targets. Material and Methods We identified differentially expressed genes (DEGs) between ccRCC and adjacent normal tissues in GEO database using a Robust Rank Aggregation (RRA) method. An mRNA signature (mRNASig) based on DEGs was developed using Cox and LASSO analysis in the TCGA database and validated in the ICGC database. Afterward, the influence of mRNASig mRNAs on the immune microenvironment in ccRCC was explored using comprehensive bioinformatics analysis. Results A total of 957 robust DEGs were identified using the RRA method. mRNASig comprised CEP55, IFI44, NCF4, and TCIRG1 and was developed and validated to identify high-risk patients who had poorer prognosis than low-risk patients. A nomogram was also constructed based on mRNASig, AJCC stage, and tumor grade. The mRNASig were closely related to a variety of tumor-infiltrating lymphocytes, especially including CD8+ T cells, activated CD4+ memory T cells, regulatory T cells, activated NK cells, and resting NK cells. The mRNASig were also correlated positively with the expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2. Conclusion We developed and validated mRNASig to assist clinicians in making personalized treatment decisions. Furthermore, CEP55, IFI44, NCF4, and TCIRG1 may be novel potential targets for future treatment of ccRCC.

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Section: Introductionmentioning

confidence: 99%

Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

Zhao

Khan

et al. 2020

Front. Genet.

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“…ccRCC accounts for 75–80% of all RCC cases and the majority of mortality cases from kidney cancer ( 2 ). Despite the availability of numerous types of treatments, ~30% of patients with ccRCC eventually develop metastasis, resulting in high mortality rates ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma

Liu

et al. 2018

Oncol Rep

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Dysregulation of C-Type Lectin Domain Family 3 Member B (CLEC3B) in serum or tumor tissues has been reported in patients with various cancer types. However, the expression and function of CLEC3B in clear cell renal cell carcinoma (ccRCC) remain unknown. To examine the function of CLEC3B in ccRCC, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were examined to determine the expression of CLEC3B at the transcriptional level and it was demonstrated that CLEC3B mRNA was significantly downregulated in ccRCC compared with normal tissues (P<0.0001 and P=0.0392 in TCGA and GEO databases, respectively). The downregulation of CLEC3B was further validated at the protein level in 78.9% of ccRCCs by immunohistochemistry. To investigate the potential genetic mechanism for CLEC3B downregulation in ccRCC, copy number analysis was performed by profiling the copy number variation data from the TCGA project and it was revealed that the copy number loss of CLEC3B was prevalent in up to 88.1% of patients with ccRCC. CLEC3B genetic deletion was coupled with the well-known genetic loss of the von Hippel-Lindau tumor suppressor, which is a characteristic oncogenic event during ccRCC carcinogenesis. The downregulation of CLEC3B was associated with tumor progression and predicted unfavorable prognostic outcomes in the TCGA cohort. Real-time cell analyzer system technology revealed that CLEC3B inhibited the proliferation of ccRCC cell lines in vitro and that the mitogen-activated protein kinase pathway may contribute to this process. CLEC3B demonstrated substantial positive associations with proliferation inhibitors, but inverse associations with proliferation inducers and markers in two large ccRCC cohorts, suggesting that CLEC3B was able to identify ccRCCs with a lower proliferation capacity. In conclusion, the results of the present study propose that CLEC3B is a promising target for therapeutic intervention in ccRCC.

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“…Complete surgical resection is considered to be a curative treatment option for RCCs at the early or locally advanced stage. However, about 30% of patients who received curative resection experience disease recurrence [ 4 ]. Despite the recent introduction of new molecular targeted agents, the prognosis of recurrent or metastatic RCC is very poor, with 5-year survival rate of about 10% [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Kim

Jang

et al. 2018

IJMS

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The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration (mutation, loss of heterozygosity, or promoter hypermethylation). However, the pathological or prognostic significance of VHL gene alteration has not been well defined. We conducted this meta-analysis to evaluate the association between VHL alteration and clinopathologic findings in ccRCCs. We performed a systematic computerized search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar (up to July 2018). From ten studies, 1,082 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features (nuclear grade and disease stage) or hazard ratios (HRs) with 95% CIs for overall survival (OS). VHL alteration was not significantly associated with nuclear grade (OR = 0.79, 95% CI: 0.59–1.06, p = 0.12) or disease stage (OR = 1.07, 95% CI: 0.79–1.46, p = 0.65). There was also no significant correlation between VHL alteration and OS (HR = 0.75, 95% CI: 0.43–1.29, p = 0.30). When we pooled HRs for OS according to the VHL alteration types, the combined HRs were 0.72 (95% CI: 0.47–1.11, p = 0.14) for VHL mutations and 1.32 (95% CI: 0.70–2.47, p = 0.39) for methylation. In conclusion, this meta-analysis indicates that VHL gene alteration is not significantly associated with the pathological features and survival in patients with ccRCC.

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Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database

Cited by 48 publications

References 17 publications

Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

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