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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
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Background: Mechanism and predictive biomarkers for tyrosine kinase inhibitor (TKI) resistance of advanced clear cell renal cell carcinoma (ccRCC) have not been fully evaluated. Methods: We performed gene expression profiling on samples from an acquired TKI resistance cohort that consisted of 10 cases of TKI-treated ccRCC patients with matched tumor tissues harvested at pre-treatment and TKI-resistant post-treatment periods. In addition, a public microarray dataset from patient-derived xenograft model for TKI-treated ccRCC (GSE76068) was retrieved. Commonly altered pathways between the datasets were investigated by Ingenuity Pathway Analysis using commonly regulated differently expressed genes (DEGs). The significance of candidate DEG on intrinsic TKI resistance was assessed through immunohistochemistry in a separate cohort of 101 TKI-treated ccRCC cases. Results: TNFRSF1A gene expression and tumor necrosis factor (TNF)-α pathway were upregulated in ccRCCs with acquired TKI resistance in both microarray datasets. Also, high expression (> 10% of labeled tumor cells) of TNF receptor 1 (TNFR1), the protein product of TNFRSF1A gene, was correlated with sarcomatoid dedifferentiation and was an independent predictive factor of clinically unfavorable response and shorter survivals in separated TKI- treated ccRCC cohort. Conclusion: TNF-α signaling may play a role in TKI resistance, and TNFR1 expression may serve as a predictive biomarker for clinically unfavorable TKI responses in ccRCC.
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참고문헌 (42)
참고문헌 신청
Moch H / 2015 / WHO Classification of Tumours of the Urinary System and Male Genital Organs / IARC :18~21
Siegel RL / 2019 / Cancer statistics, 2019 / CA Cancer J Clin 69(1):7~34
Okada A / 2002 / Recent advances in pathophysiology and surgical treatment of congenital dilatation of the bile duct / J Hepatobiliary Pancreat Surg 9(3):342~351
Rao A / 2018 / Survival outcomes for advanced kidney cancer patients in the era of targeted therapies / Ann Transl Med 6(9):165
Rini BI / 2009 / Resistance to targeted therapy in renal-cell carcinoma / Lancet Oncol 10(10):992~1000
Siegel RL / 2019 / Cancer statistics, 2019 / CA Cancer J Clin 69(1):7~34
Okada A / 2002 / Recent advances in pathophysiology and surgical treatment of congenital dilatation of the bile duct / J Hepatobiliary Pancreat Surg 9(3):342~351
Rao A / 2018 / Survival outcomes for advanced kidney cancer patients in the era of targeted therapies / Ann Transl Med 6(9):165
Rini BI / 2009 / Resistance to targeted therapy in renal-cell carcinoma / Lancet Oncol 10(10):992~1000
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