Serum Interleukin-6 Levels in Metastatic Renal Cell Carcinoma Before Treatment With Interleukin-2 Correlates With Paraneoplastic Syndromes but Not Patient Survival

Walther, McClellan M.; Johnson, Bruce; Culley, Donald; Shah, Reena; Weber, J.; Venzon, David; Yang, James Chih‐Hsin; Linehan, W. Marston; Rosenberg, Steven A.

doi:10.1016/s0022-5347(01)63709-1

Cited by 64 publications

(26 citation statements)

References 27 publications

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“…IL-6 expression, meanwhile, was 19.88-fold upregulated in the Caki-1 cell line. mRCC (40,74). STATs are a family of cytoplasmic proteins that take part in transcription of genes involved in diverse cellular activities in disease states (8,44), and the expression of STAT1, STAT2, STAT4, and STAT6 genes was observed to be elevated (4.86, 4.25, 3.48, and 3.03, respectively) in Caki-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

Khan

Dębski

Dąbrowski

et al. 2016

American Journal of Physiology-Renal Physiology

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Section: Discussionmentioning

confidence: 99%

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

Khan

Dębski

Dąbrowski

et al. 2016

American Journal of Physiology-Renal Physiology

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“…In samples with a positive MSP band, the relative methylation ratio was determined after the MSP or USP product was electrophoresed in nondenaturing 12% polyacrylamide gels. The area under the curve (AUC) corresponding to each band was calculated using ImageJ software, 4 and the relative methylation level was determined [MSP ratio = MSP band density / (MSP band density + USP band density)] as reported previously (17,18).…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, f10% of patients with locally confined tumors die of disease progression within 5 years of nephrectomy (3). Although several prognostic variables for RCC, such as serum interleukin-6 or immunosuppressive acid protein, have been proposed, they have not been shown to be reliable tumor markers due to low specificity and sensitivity (4,5). Therefore, accurate preoperative prognostic biomarkers are needed to distinguish highly malignant RCCs to aggressively treat them or put them under stringent surveillance.…”

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confidence: 99%

Wnt Antagonist Family Genes as Biomarkers for Diagnosis, Staging, and Prognosis of Renal Cell Carcinoma Using Tumor and Serum DNA

Urakami

Shiina

Enokida

et al. 2006

Clinical Cancer Research

129

106

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Purpose: We hypothesized that combined methylation analysis of Wnt antagonist genes could serve as a panel of biomarkers for diagnosis, staging, and prognosis in renal cell carcinoma (RCC). Experimental Design: Samples (n = 62) of RCC and corresponding normal renal tissue (NRT) were analyzed using methylation-specific PCR for methylation of six Wnt antagonist genes (sFRP-1, sFRP-2, sFRP-4, sFRP-5, Wif-1, and Dkk-3). To increase the sensitivity/specificity of RCC detection, the methylation score (M score) for multigene methylation analysis was developed. Receiver operator characteristic curve analysis was used to determine the optimal sensitivity/specificity of the M score. In addition, the M score was compared with the clinicopathologic outcome.Thirty-three serum DNA samples were also used to investigate the methylation status of Wnt antagonist genes. Results: The methylation levels of all Wnt antagonists were significantly higher in RCC than in NRT. In multivariate regression analysis, the methylation level of sFRP-1was a significant independent predictor of RCC, whereas for sFRP-2 and sFRP-4 there was a trend toward significance as independent predictors. The M score of Wnt antagonist genes was significantly higher in RCC than in NRT. Overall, the M score had a sensitivity of 79.0% and a specificity of 75.8% (area under the curve, 0.808) as a diagnostic biomarker. In addition, the M score could significantly distinguish grade, pTcategory, M category, and overall survival of RCC patients.The M score was independent of age and gender in predicting overall survival by the Cox proportional hazards model. In RCC patients, 72.7% of the methylation-specific PCR results had identical methylation in samples of tumor and serum DNA. No serum DNA in normal controls showed aberrant methylation of the Wnt antagonist genes. In addition, the methylation status of Wnt antagonist genes in serum DNA was significantly correlated with tumor grade and stage. Conclusions: This is the first report showing that M score analysis of Wnt antagonist genes can serve as an excellent epigenetic biomarker panel for detection, staging, and prognosis of RCC using serum DNA.

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“…Previous large scale studies on IL-2 treatment have shown that pretreatment high inflammatory activation, measured by markers such as IL-6 and CRP, predicts lack of IL-2 activity on tumour objective response and its efficacy on overall survival in metastatic cancer patients (Blay et al, 1992;Tartour et al, 1994). However, a separate, smaller study demonstrated that detectable IL-6 serum levels correlated with paraneoplastic syndromes but not with response or survival (Walther et al, 1998). Regarding lymphocyte count changes, some studies (Palmer et al, 1993;Gohring et al, 1996) demonstrated that a greater lymphocyte increase after s.c. IL-2 administration occurrs in metastatic renal cell cancer patients with objective response.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment serum markers and lymphocyte response to interleukin-2 therapy

et al. 1999

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Summary Lymphocytosis is a marker of subcutaneous interleukin (IL)-2 therapy efficacy, whereas baseline elevated inflammatory indices were noticed in IL-2-resistant disease. The aim of this study was to analyse the relationship between pretreatment circulating values of IL-6, neopterin, sIL-2R, ESR and the changes in lymphocyte number in response to IL-2 administration. Twenty metastatic renal cell cancer patients were treated with subcutaneous IL-2 immunotherapy (6 000 000 IU day -1 for 6 days per week for 4 weeks); tumour response consisted of partial response (PR) in four patients, stable disease (SD) in eight patients and progressive disease (PD) in eight patients. Abnormally high pretreatment values of each marker were found as follows: IL-6 in seven patients, neopterin in nine patients, sIL-2R in 13 patients. In response to IL-2 immunotherapy, a significantly higher mean increase in lymphocyte number and a higher percentage of patients with tumour response or stable disease were observed when pretreatment values of IL-6, neopterin and sIL-2R were within the normal range, in comparison to patients with high values for these markers. The pretreatment excess of these serum inflammatory markers seems to negatively influence both the host and tumour response to IL-2 administration, by preventing the IL-2-induced lymphocytosis and resulting in tumour progression. Further studies are requested to verify if overall survival and quality of life may depend on pretreatment host immune status and/or lymphocyte response after IL-2 administration.

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Serum Interleukin-6 Levels in Metastatic Renal Cell Carcinoma Before Treatment With Interleukin-2 Correlates With Paraneoplastic Syndromes but Not Patient Survival

Cited by 64 publications

References 27 publications

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line

Wnt Antagonist Family Genes as Biomarkers for Diagnosis, Staging, and Prognosis of Renal Cell Carcinoma Using Tumor and Serum DNA

Pretreatment serum markers and lymphocyte response to interleukin-2 therapy

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