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- Genitourinary Cancer
- Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
- Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
- Cancer Res Treat. 2021;53(4):1174-1183. Published online March 17, 2021
- DOI: https://doi.org/10.4143/crt.2021.031
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Abstract
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Supplementary Material
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ePub - Purpose
Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs.
Materials and Methods
All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation.
Results
FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival.
Conclusion
FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC. -
Citations
Citations to this article as recorded by
- Differences in genomic profile of high-grade urothelial carcinoma according to tumor location
Cheol Keun Park, Nam Hoon Cho
Urologic Oncology: Seminars and Original Investigations.2022; 40(3): 109.e1. CrossRef - The Role of Iron in Cancer Progression
Qianqian Guo, Liwen Li, Shanshan Hou, Ziqiao Yuan, Chenhui Li, Wenzhou Zhang, Lufeng Zheng, Xiaoman Li
Frontiers in Oncology.2021;[Epub] CrossRef
- Differences in genomic profile of high-grade urothelial carcinoma according to tumor location
- 5,889 View
- 137 Download
- 3 Web of Science
- 2 Crossref
- Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study
- Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim
- Cancer Res Treat. 2018;50(2):488-494. Published online May 22, 2017
- DOI: https://doi.org/10.4143/crt.2016.584
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC. -
Citations
Citations to this article as recorded by- Advances in non‐clear cell renal cell carcinoma management: From heterogeneous biology to treatment options
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- Advances in non‐clear cell renal cell carcinoma management: From heterogeneous biology to treatment options
- 10,576 View
- 490 Download
- 35 Web of Science
- 26 Crossref
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