Differential expressions of PD-1, PD-L1, and PD-L2 between the primary and metastatic sites in renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 616-616
Author(s):  
Xingming Zhang ◽  
Pengfei Shen ◽  
Hao Zeng

616 Background: To evaluate the differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastatic sites of renal cell carcinoma (RCC), and to find potential factors influencing expression difference. Methods: We included cases of RCC histologically diagnosed at West China Hospital between January 2009 and November 2016. Clinicopathological data were retrospectively extracted. SPPS 22.0 and GraphPad Prism 6 statistical software were used for data analysis. Kaplan-Meier was used to analyze PFS and OS. R software was used to calculate predictive accuracy (PA). Results: A total of 163 patients were included in this study. Immunohistochemistry results suggested significant differential expressions of PD-1, PD-L1 and PD-L2 between the primary and metastasis, with a higher detection rate of the primary than metastasis. Meanwhile, the concordance rate of PD-L1 between the primary and metastasis was only 32.5% (27/83), with a significant statistically difference (χ2 = 4.664, p = 0.031) and poor consistency (Kappa = 0.229, p = 0.031). PD-1 and PD-L1 were highly expressed in the lung/lymph node and PD-L2 was highly expressed in visceral metastases. Survival analysis suggested that PD-1 positive either in the primary or metastasis was a poor prognostic factor for OS (HR: 1.59, 95% CI 1.08-2.36, P = 0.0195). The expression of PD-L1 in the primary was a poor prognostic factor for OS (HR 2.55, 95% CI 1.06-6.15, P = 0.0373). Although the predictive effect of PD-L1 expression on OS was not statistically significant in TKI treated patients, the OS time was shorter in PD-L1-positive patients than those negative (median OS 19.0 vs 41.0 months). In the whole cohort, the PA value of COX regression analysis was 0.683 for PFS, and the addition of PD-1 expression in the primary increased the PA value to 0.699. Conclusions: The assessment of immunological checkpoint-related protein in primary tumor may not be able to provide adequate information for clinicians to evaluate or predict the patient's treatment-related efficacy and prognosis. Biopsy or resection of the metastases may provide a more accurate biological information for clinician's decision-making and the patient's prognosis.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Minyong Kang ◽  
Seung Jea Shin ◽  
Hyun Hwan Sung ◽  
Hwang Gyun Jeon ◽  
Byong Chang Jeong ◽  
...  

Background. This study is aimed at examining the prognostic role of pre-to-postoperative dynamics of De Ritis ratio (aspartate aminotransaminase (AST)/alanine aminotransaminase (ALT)) in patients with nonmetastatic renal cell carcinoma (RCC) following radical nephrectomy. Methods. We retrospectively reviewed the records of 670 patients who underwent radical nephrectomy for nonmetastatic RCC between 1996 and 2012 at our institution. The cutoff points for preoperative (=1.0) and postoperative AST/ALT ratios (=1.12) were assigned based on the median values. We categorized patients into four groups according to the dynamics of AST/ALT ratios: group 1 (lower (≤1.0) ⟶ lower (≤1.12)), group 2 (lower (≤1.0) ⟶ higher (>1.12)), group 3 (higher (>1.0) ⟶ lower (≤1.12)), and group 4 (higher (>1.0) → higher (>1.12)). Results. When grouped by a preoperative AST/ALT ratio alone, the groups were not statistically different in cancer-specific survival (CSS) or overall survival (OS). In contrast, in Kaplan-Meier analysis, CSS (P=0.0296) and OS (P=0.0324) were both significantly shorter with an increased postoperative AST/ALT ratio. According to the pre-to-postoperative dynamics of the AST/ALT ratio, group 2 (lower (≤1.0) ⟶ higher (>1.12)) had a significantly lower CSS (P=0.0028) and OS (P=0.0194) than the other groups. On multivariate Cox regression analysis, the pre-to-postoperative dynamics of the AST/ALT ratio were a significant prognostic factor for CSS (hazard ratio, HR=3.45) and OS (HR=2.18). Conclusion. This study is the first to suggest that the dynamics of the pre-to-postoperative De Ritis ratio represent an independent prognostic factor for RCC patients following nephrectomy.


2007 ◽  
Vol 25 (7) ◽  
pp. 845-851 ◽  
Author(s):  
Thomas Kleinrath ◽  
Christoph Gassner ◽  
Peter Lackner ◽  
Martin Thurnher ◽  
Reinhold Ramoner

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.


2020 ◽  
Vol 69 (10) ◽  
pp. 2041-2051 ◽  
Author(s):  
Ryosuke Jikuya ◽  
Takeshi Kishida ◽  
Masahiko Sakaguchi ◽  
Tomoyuki Yokose ◽  
Masato Yasui ◽  
...  

2021 ◽  
pp. 1-8
Author(s):  
Fatma Bugdayci Basal ◽  
Cengiz Karacin ◽  
Irem Bilgetekin ◽  
Omur Berna Oksuzoglu

Introduction: The aim of the study was to evaluate impact of the systemic immune-inflammation index (SII) on prognosis and survival within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score groups. Methods: The records of 187 patients with metastatic renal cell carcinoma (RCC) were reviewed retrospectively. The SII was calculated as follows: SII = Neutrophil × Platelet/Lymphocyte. The patients were categorized into 2 groups based on a median SII of 730 (×109 per 1 L) as SII low (<730) and SII high (≥730). The Kaplan-Meier method was used for survival analysis and a Cox regression model was utilized to determine independent predictors of survival. Results: The median age was 61 years (range: 34–86 years). Kaplan-Meier tests revealed significant differences in survival between the SII-low and SII-high levels (27.0 vs. 12.0 months, respectively, p < 0.001). The Cox regression model revealed that SII was an independent prognostic factor. The implementation of the log-rank test in the IMDC groups according to the SII level provided the distinction of survival in the favorable group (SII low 49.0 months vs. SII high 11.0 months, p < 0.001), in the intermediate group (SII low 26.0 vs. SII high 15.0 months, p = 0.007), and in the poor group (SII low 19.0 vs. SII high 6.0 months, p = 0.019). Conclusion: The SII was an independent prognostic factor and provided significant differences in survival for the favorable, intermediate, and poor IMDC groups. Thus, the SII added to the IMDC score may be clinically beneficial in predicting survival.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 684-684
Author(s):  
Igor Stukalin ◽  
Shaan Dudani ◽  
Connor Wells ◽  
Chun Loo Gan ◽  
Sumanta K. Pal ◽  
...  

684 Background: Immuno-Oncology (IO) combinations are standard of care first-line treatment for metastatic renal cell carcinoma (mRCC). Data on therapy with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) post-progression on IO-combination therapy are limited. Methods: Using the IMDC, a retrospective analysis was done on mRCC patients treated with second-line VEGF TKIs after receiving IO combination therapy. Patients received first-line ipilimumab+nivolumab (IOIO) or anti-PD(L)1+anti-VEGF (IOVE). Baseline variables and second-line IMDC risk factors were collected. Overall response rates (ORR), time to treatment failure (TTF) and overall survival (OS) were determined. Multivariable Cox regression analysis was performed. Results: 142 patients were included. 75 patients received IOIO and 67 received IOVE pretreatment. The ORR of 2nd line therapy was 17/46 (37%) and 7/57 (12%) in the IOIO and IOVE pretreated groups, respectively (p<0.01). 2nd-line TTF was 5.4 months (95% CI 4.1-8.3) for the IOIO- and 4.6 months (95% CI 3.7-5.8) for the IOVE-pretreated group (p=0.37). 2nd-line median OS was 17.2 months (95% CI 10.8-35.1) and 11.8 months (95% CI 9.9-21.3) for the prior IOIO and IOVE groups, respectively (p=0.13). The hazard ratio adjusted by IMDC for IOVE vs IOIO pretreatment was 1.22 (95% CI 0.73-2.07, p=0.45) for 2nd line TTF and 1.43 (95% CI 0.74-2.8, p=0.29) for 2nd line OS. Conclusions: VEGF TKIs show activity after combination IO therapy. Response rates are higher in patients treated with VEGF TKIs after first-line IOIO compared to after IOVE. In patients with VEGF TKI after IOIO or IOVE, no difference in OS and TTF was observed.[Table: see text]


2014 ◽  
Vol 10 (8) ◽  
pp. 1361-1372 ◽  
Author(s):  
Paolo Grassi ◽  
Elena Verzoni ◽  
Luca Porcu ◽  
Isabella Testa ◽  
Roberto Iacovelli ◽  
...  

Author(s):  
A.D. Volkohon ◽  
V. Yu. Harbuzova ◽  
O.V. Ataman

Today, the long non-coding RNA MALAT1 is considered to be one of the major RNAs involved in the emergence and metastasizing of various malignant tumours. Recent experiments have shown that MALAT1 plays an important role in the onset and progression of kidney cancer as well. It was found that cancer patient survival depends on the level of MALAT1 gene expression. The aim of the study was to investigate the possible association between rs3200401 MALAT1 gene polymorphism and age of kidney cancer onset among Ukrainian patients. Materials and methods. The venous blood of 101 patients with clear cell renal cell carcinoma (42 women and 59 men) was used for study. Determination of MALAT1 gene rs320040 polymorphism was performed by the Real-Time polymerase chain reaction method using TaqManSNP Assay C_3246069_10 components. Statistical analysis of the data obtained was performed using SPSS (version 17.0). To test the possible association between rs3200401 genotypes and the age of kidney cancer onset Kaplan-Meier and Cox regression techniques were used. P value < 0.05 was considered as statistically significant. Results. The obtained results of MALAT1 gene rs3200401 polymorphic site genotyping revealed that 71 (70.3%) patients with renal cell carcinoma had CC genotype, 29 (28.7%) – CT, 1 (1%) – TT genotype. Survival analysis by Kaplan-Meier method showed that life expectancy until the tumour occurrence was not related to rs3200401 locus (log rank P = 0.449 – for codominant model; log rank P = 0.847 – for dominant model). The results of Cox regression analysis also showed no link between MALAT gene rs3200401-site and risk of renal cell carcinoma development (P > 0.05). No statistically significant results were found after adjustment for sex, body mass index, metastasis, smoking and drinking habits (P > 0.05). Conclusions. The rs3200401 gene polymorphism of long non-coding RNA MALAT1 is not associated with the age of kidney cancer onset in Ukrainian population.


2021 ◽  
Vol 8 ◽  
Author(s):  
Weipu Mao ◽  
Nieke Zhang ◽  
Keyi Wang ◽  
Qiang Hu ◽  
Si Sun ◽  
...  

We conducted a multicenter clinical study to construct a novel index based on a combination of albumin-globulin score and sarcopenia (CAS) that can comprehensively reflect patients' nutritional and inflammatory status and assess the prognostic value of CAS in renal cell carcinoma (RCC) patients. Between 2014 and 2019, 443 patients from 3 centers who underwent nephrectomy were collected (343 in the training set and 100 in the test set). Kaplan-Meier curves were employed to analyze the impact of albumin-globulin ratio (AGR), albumin-globulin score (AGS), sarcopenia, and CAS on overall survival (OS) and cancer-specific survival (CSS) in RCC patients. Receiver operating characteristic (ROC) curves were used to assess the predictive ability of AGR, AGS, sarcopenia, and CAS on prognosis. High AGR, low AGS, and nonsarcopenia were associated with higher OS and CSS. According to CAS, the training set included 60 (17.5%) patients in grade 1, 176 (51.3%) patients in grade 2, and 107 (31.2%) patients in grade 3. Lower CAS was linked to longer OS and CSS. Multivariate Cox regression analysis revealed that CAS was an independent risk factor for OS (grade 1 vs. grade 3: aHR = 0.08; 95% CI: 0.01–0.58, p = 0.012; grade 2 vs. grade 3: aHR = 0.47; 95% CI: 0.25–0.88, p = 0.018) and CSS (grade 1 vs. grade 3: aHR = 0.12; 95% CI: 0.02–0.94, p = 0.043; grade 2 vs. grade 3: aHR = 0.31; 95% CI: 0.13–0.71, p = 0.006) in RCC patients undergoing nephrectomy. Additionally, CAS had higher accuracy in predicting OS (AUC = 0.687) and CSS (AUC = 0.710) than AGR, AGS, and sarcopenia. In addition, similar results were obtained in the test set. The novel index CAS developed in this study, which reflects patients' nutritional and inflammatory status, can better predict the prognosis of RCC patients.


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