Dataset Information

Survival and clinical prognostic factors in metastatic non-clear cell renal cell carcinoma treated with targeted therapy: A multi-institutional, retrospective study using the Korean metastatic renal cell carcinoma registry.

ABSTRACT:

Objectives

The optimal treatment strategy for metastatic non-clear cell renal cell carcinoma (mNCCRCC) is still elusive and mainly extrapolated from evidence available for metastatic clear cell renal cell carcinoma. The aim of the study was therefore to investigate the survival outcomes and prognostic factors affecting survival in patients with mNCCRCC treated with targeted therapy.

Materials and methods

We analyzed a total of 156 patients (8.1%) with mNCCRCC among the total cohort of 1922 patients in the Korean metastatic RCC registry. We used Kaplan-Meier curve analysis to calculate the survival estimates for first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS). We also used the log-rank test to compare the different groups and multivariate Cox-proportional hazard regression analyses to evaluate the prognostic factors for survival.

Results

The mNCCRCC group had significantly inferior survival outcomes in terms of first-line PFS, total PFS, and CSS (all P < 0.05). We found survival benefits in patients treated with first-line vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs, first-line PFS, and total PFS, all P < 0.05), cytoreductive nephrectomy (CSS, P < 0.0001), metastasectomy (CSS, P = 0.0017), and patients with metachronous metastasis (first-line PFS, total PFS, and CSS, all P < 0.05). Liver metastasis was the only significant prognostic factor for both first-line PFS and CSS (all P < 0.05).

Conclusions

In the current targeted therapy era, survival of mNCCRCC is still inferior in comparison with that of mCCRCC patients. We found survival benefits in patients treated with first-line VEGF-TKIs/CN/metastasectomy, and metachronous metastasis patients.

SUBMITTER: Kim JK

PROVIDER: S-EPMC6601573 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Survival and clinical prognostic factors in metastatic non-clear cell renal cell carcinoma treated with targeted therapy: A multi-institutional, retrospective study using the Korean metastatic renal cell carcinoma registry.

Kim Jung Kwon JK Kim Sung Han SH Song Mi Kyung MK Joo Jungnam J Seo Seong Il SI Kwak Cheol C Jeong Chang Wook CW Song Cheryn C Hwang Eu Chang EC Seo Ill Young IY Lee Hakmin H Hong Sung-Hoo SH Park Jae Young JY Chung Jinsoo J

Cancer medicine 20190509 7

<h4>Objectives</h4>The optimal treatment strategy for metastatic non-clear cell renal cell carcinoma (mNCCRCC) is still elusive and mainly extrapolated from evidence available for metastatic clear cell renal cell carcinoma. The aim of the study was therefore to investigate the survival outcomes and prognostic factors affecting survival in patients with mNCCRCC treated with targeted therapy.<h4>Materials and methods</h4>We analyzed a total of 156 patients (8.1%) with mNCCRCC among the total cohor ...[more]

PMID: 31070307

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Project description:Renal cell carcinoma (RCC) is one of the leading causes of cancer-related death worldwide. Tumour metastasis and heterogeneity lead to poor survival outcomes and drug resistance in patients with metastatic RCC (mRCC). In this study, we aimed to assess intratumoural heterogeneity (ITH) in mRCC cells by performing a combined analysis of bulk data and single-cell RNA-sequencing data, and develop novel biomarkers for prognosis prediction on the basis of the potential molecular mechanisms underlying tumorigenesis. Eligible single-cell cohorts related to mRCC were acquired using the Gene Expression Omnibus (GEO) dataset to identify potential mRCC subpopulations. We then performed gene set variation analysis to understand the differential function in primary RCC and mRCC samples. Subsequently, we applied weighted correlation network analysis to identify coexpressing gene modules that were related to the external trait of metastasis. Protein-protein interactions were used to screen hub subpopulation-difference (sub-dif) markers (ACTG1, IL6, CASP3, ACTB and RAP1B) that might be involved in the regulation of RCC metastasis and progression. Cox regression analysis revealed that ACTG1 was a protective factor (HR < 1), whereas the other four genes (IL6, CASP3, ACTB and RAP1B) were risk factors (HR > 1). Kaplan-Meier survival analysis suggested the potential prognostic value of these sub-dif markers. The expression of sub-dif markers in mRCC was further evaluated in clinical samples by immunohistochemistry (IHC). Additionally, the genetic features of sub-dif marker expression patterns, such as genetic variation profiles, correlations with tumour-infiltrating lymphocytes (TILs), and targeted signalling pathway activities, were assessed in bulk RNA-seq datasets. In conclusion, we established novel subpopulation markers as key prognostic factors affecting EMT-related signalling pathway activation in mRCC, which could facilitate the implementation of a treatment for mRCC patients.

Dataset Information

Survival and clinical prognostic factors in metastatic non-clear cell renal cell carcinoma treated with targeted therapy: A multi-institutional, retrospective study using the Korean metastatic renal cell carcinoma registry.

Objectives

Materials and methods

Results

Conclusions

Publications

Survival and clinical prognostic factors in metastatic non-clear cell renal cell carcinoma treated with targeted therapy: A multi-institutional, retrospective study using the Korean metastatic renal cell carcinoma registry.

Similar Datasets

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