Effect of EGR1/LIPT1 regulatory axis on cuproptosis in chromophobe renal cell carcinoma

Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

Differences in Organ System of Distant Metastasis by Renal Cell Carcinoma Subtype

Cytogenetic and molecular genetic techniques have been used in demonstrating the chromosomal abnormalities which characterize specific subtypes of renal cell carcinoma (RCC). The aim of this study was to determine the efficiency of fluorescent in situ hybridization (FISH) technique in characterizing various subtypes of RCC based on the presence of specific chromosome abnormalities found in each RCC subtype. FISH was performed on touch imprint smears from eight renal cell carcinomas histologically confirmed by established criteria. In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase FISH was performed using centromeric probes for chromosomes 1, 2, 6, 10, 12, 17 and 21. All four ChRCC tumors showed one FISH signal corresponding to one copy number for each of these chromosomes. Two papillary RCCs included in this study showed trisomy 7 and 17, and loss of chromosome Y, using the corresponding chromosome centromeric probes. Similarly, we tested two clear cell RCCs for chromosome 3 short arm deletion with DNA probe 3p21.3. Both tumors showed loss of 3p21.3 signal. We conclude that interphase FISH performed on touch imprint smears is a relatively simple, rapid and reliable method for detecting chromosome abnormalities which are specific for various subtypes of RCC.

Multiple therapeutic options for renal tumors that are now available have put pathologists under increasing pressure to render diagnosis on limited material. Results on biopsies by hematoxylin and eosin (H&E) have historically not been encouraging. Currently, multiple immunohistochemical markers with differential expression in these renal tumors are available. We studied the utility of such markers on needle biopsies that were obtained ex vivo. After nephrectomy, two 18-guage cores were obtained and processed routinely. Expressions of carbonic anhydrase (CA) IX, CD117, α-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), and CD10 were evaluated. Results, with or without immunostaining, were compared with the final nephrectomy diagnosis. We studied 145 tumors, including 119 renal cell carcinomas (83 clear cell, 18 papillary, 14 chromophobe, and 4 type unclassified), 11 oncocytomas, and 15 miscellaneous tumors. Adequate evaluable material was present in 123 (85%) cases. In such biopsies, 81% of cases were correctly classified by H&E alone, with correct diagnosis in 90% of cases in the most common tumor subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma). By adding immunostains, the accuracy was 90% overall and 99% among the 4 most common subtypes. The following extent and patterns of immuneexpression were highly useful in the diagnoses: diffuse, membranous CAIX expression in clear cell renal cell carcinoma, diffuse positivity for AMACR in papillary renal cell carcinoma, distinct peripheral cytoplasmic accentuation for CD117 in chromophobe renal cell carcinoma, widespread and intense positivity for CK7 in chromophobe and papillary renal cell carcinoma, and diffuse membranous reactivity in clear cell and patchy/luminal in papillary renal cell carcinoma for CD10. In conclusion, utilizing immunostains improves classification of renal tumors on needle biopsy, which may be of particular help for pathologists with limited experience. Both extent and patterns must be considered for a definitive diagnosis.

Head-to-head comparison of all the prognostic models recommended by the European Association of Urology Guidelines to predict oncologic outcomes in patients with renal cell carcinoma

To retrospectively evaluate the ability of multiparametric magnetic resonance (MR) imaging to differentiate renal tumours. MR images from 100 consecutive pathologically proven solid renal tumours without macroscopic fat [57 clear cell, 16 papillary and 7 chromophobe renal cell carcinomas (RCCs), 16 oncocytomas and 4 minimal fat angiomyolipomas (AMLs)] between 2009 and 2012 were evaluated. Two radiologists blinded to pathology results independently reviewed double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash-out indices (WoI) between different phases were calculated. There were significant differences between papillary RCCs and other renal tumours for arterial WiI (P < 0.001), initial WoI (P = 0.006) and ADC ratio (P < 0.001); between chromophobe RCCs and oncocytomas for TSR (P = 0.02), parenchymal WiI (P = 0.03), late WiI (P = 0.02), initial WoI (P = 0.03) and late WoI (P = 0.04); and between clear cell RCCs and oncocytomas for SII (P = 0.01) and parenchymal WiI (P = 0.01). Papillary RCCs were distinguished from other tumours (sensitivity 37.5 %, specificity 100 %) and oncocytomas from chromophobe RCCs (sensitivity 25 %, specificity 100 %) and clear cell RCCs (sensitivity 100 %, specificity 94.2 %). MR imaging provides criteria able to accurately distinguish papillary RCCs from other tumours and oncocytomas from chromophobe and clear cell RCCs. • Multiparametric MR parameters accurately distinguish papillary RCCs with high specificity (100 %). • Oncocytomas can be distinguished from chromophobe RCCs with high specificity (100 %). • Oncocytomas can be distinguished from clear cell RCCs with high specificity (94.2 %). • In oncocytomatosis, imaging follow-up with such parameters analysis could be promoted.

Background: Renal cell carcinoma (RCC) represents a heterogeneous group of cancers that arise from the nephron and are subtyped by histopathological features. The most common subtypes are clear cell RCC (~75%) and papillary RCC (~15%); whereas chromophobe renal cell carcinoma (ChRCC) represents only 5% of RCC cases. ChRCC typically demonstrate a well-known karyotype of multiple chromosomal losses and a relatively indolent pattern of local growth, but can present with aggressive features and demonstrate resistance to treatment in a metastatic setting. Some ChRCC cases demonstrate regions of sarcomatoid RCC and the exact cause of this differentiation has yet to be elucidated. Cell line models are an important tool for both the investigation of tumor biology and therapeutic drug efficacy. Currently, numerous cell lines models exist that have been derived from sporadic clear cell or papillary RCCs, but there are few cell lines derived from chromophobe RCCs and none are well characterized. This study produced a novel ChRCC-derived cell line model and provides an initial genetic and metabolic characterization. Materials and Methods: A patient presented with a 20 cm ChRCC with regions of sarcomatoid differentiation that was surgically excised and a section of this tumor was used to establish a spontaneously immortal cell line model, UOK276. This line was grown for over 20 passages and cytogenetically assessed by spectral karyotyping (SKY). Mutation analysis was performed using a cancer gene specific chip, OncoVar V3, which analyses 232 genes. Identified mutations were confirmed in both UOK276 and the original tumor tissue and further investigated for their effects of mRNA and protein expression. UOK276 cells were injected into nude mice to assess the production of xenograph tumors. The metabolic, bioenergetic profile was assessed using a Seahorse XF96 Extracellular Flux Analyzer. Results: The chromosomal SKY analysis did not demonstrate the classic pattern of chromophobe chromosomal losses, but demonstrated hyper-aneuploidy, with a modal number of 49 chromosomes per cell, and identified a balanced translocation t(X;8)(q10;q24). The break on chromosome 8q occurred near the MYC gene, but break-apart FISH analysis demonstrated no alterations to MYC although amplification of this derivative chromosome was observed and increased MYC mRNA expression was demonstrated. Mutation analysis identified a missense mutation (p.H193Y) of TP53, commonly mutated in ChRCC, which was only present in the sarcomatoid region of the tumor. Mutation of TP53 has previously been associated with sarcomatoid differentiation. Protein expression analysis demonstrated the presence of the mutant TP53 protein in UOK276. A heterozygous germline mutation in TRAF7 was identified resulting in an in-frame loss of 4 amino acids (del T22-P25) that was homozygous in the sarcomatoid tumor region and UOK276. Xenograph tumors were successfully grown in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The recent TCGA study of ChRCC demonstrated increased expression of the electron transport chain (ETC) genes suggesting increased oxidative phosphorylation within these tumors. Metabolic analysis of UOK276 demonstrated a relatively low level of oxygen consumption (OCR) in comparison to a normal kidney cell line and this was supported by mRNA expression data showing normal or reduced levels of expression for several ETC-related genes. Conclusions: Our study has produced a novel ChRCC cell line model that exhibits a TP53 mutation, commonly seen in ChRCC, and represents a sarcomatoid differentiated region of the tumor. UOK276 should provide a unique in vitro and in vivo preclinical model system for studying the deregulated pathways and testing therapeutic strategies in sarcomatoid differentiated ChRCC. Citation Format: Youfeng Yang, Cathy D. Vocke, Christopher J. Ricketts, Darmood Wei, Hesed M. Padilla-Nash, Shawna L. Boyle, Robert Worrell, Thomas Ried, Maria J. Merino, W. Marston Linehan. A novel cell line model for chromophobe renal cell carcinoma, UOK276, derived from an aggressive sarcomatoid differentiated tumor. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A19.

421 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer. It is required a better understanding of signalling pathways involved in renal cells. Methods: We assessed using immunohistochemistry (IHC) and quantitative real-time PCR (qPCR) with SYBR Green the profile of predictive markers involved in the cascade of events leading to the formation and progression: invasiveness, angiogenesis and antiapoptotic mechanisms. 80 RCC tissues were detected by IHC. RNA of quality only was obtained in 72 (80% clear RCC, 10% papillary RCC and 10% chromophobe RCC) to carry out the study of gene expression through qPCR. A pool of normal kidney-derived RNA samples (N=5) was used as healthy control. GAPDH and YWHAZ were used as reference genes. GenEx software was used for qPCR data processing and analysis. Nonparametric tests (Pearson’s correlation coefficient test and Spearman’s rho test, Kruskal — Wallis and Mann — Whitney) were applied for statistical data analysis (SPSS 19). Results: p53 showed higher expression in those cases with Furhman grade I (p=0.036). Moreover p53 showed a positive association with VEGF, GLUT1, GLUT4, VEGFR-2 and VHL (r=0.241, sig. level 0.05; r=0.291, sig. level 0.01; r=0.456, sig. level 0.01; r=0.187, sig. level 0.097 and Spearman’s rho=0.269, sig. level 0.05 respectively). Hif1- α, Hif1- β, Notch1 and Notch3 were upregulated in chromophobe RCC (p=0.045, p=0.03, p=0.03 and p=0.02 respectively). Hif1- α and Notch3 were upregulated in clear RCC (p=0.034 and p=0.041 respectively). Spearman’s correlation coefficient showed a strong positive correlation between Nocth1-4 members and their receptors and Hif1-α and β genes. Highlight the correlation found between: Notch1 and Hif1-α (Spearman’s rho = 0.740, significance level 0.01) and Hif1-β and Jagged1 (Spearman’s rho = 0.752, significance level 0.01). Conclusions: The pathway involving the tumor suppressor gene p53 could regulate tumor angiogenesis. Co-expression of Notch receptors, their ligands and Hif-1 α and Hif1- β subunits may play a role in human RCC. Notch cascade may represent a novel and therapeutically accessible pathway in chromophobe and clear RCC. More detailed studies of these crossing pathways are in progress.

Objective To analyze the value of multi-slice spiral CT (SCT) scan in staging and subtyping of renal cell carcinoma (RCC). Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients with RCC were retrospectively analyzed. The patients′ ages ranged from 33-78 years (average 54 years). There were 44 males and 20 females in the study group. According to the CUA Guidelines, the staging and subtyping of RCC were performed through the combined information of preoperative SCT attenuation in unenhanced, corticomedullary phase and enhancement pattern. The results were compared with the postoperative histopathological results. Results The SCT results showed 38 cases were clear cell RCC, 14 cases were papillary RCC and 12 cases were chromophobic cell RCC. Histopathological results showed that 40 cases were clear cell RCC, 16 cases were papillary RCC and 8 cases were chromophobic cell RCC. According to the standard of 40 HU of CT attenuation value, the sensitivity, specificity and accuracy were 75%, 79% and 78% for diagnosis of papillary RCC in the unenhanced phase. The sensitivity, specificity and accuracy by the standard of 90 HU of CT attenuation value was 90%, 88% and 89% for diagnosis of clear cell RCC in the corticomedullary phase. In chromophobic RCC, homogeneous enhancement was more common than in papillary RCC and clear cell RCC. There was no significant difference of staging and subtyping of RCC between SCT and pathological results (P>0.05). The accuracy of SCT in staging and subtyping of RCC was 88% in staging, and 89% in subtyping. Conclusions SCT is a useful preoperative tool to stage and subtype RCC Key words: Kidney neoplasms; Carcinoma; Tomography, X-ray computed; Neoplasm staging

The clinical staging of renal cortical tumors traditionally has not evaluated the potential effect of histological subtypes on survival. Evidence suggests that conventional clear cell renal cell carcinoma (RCC) and nonconventional clear cell RCC (chromophobe and papillary) have different metastatic potential. Using a large renal tumor database, we examined the effect of tumor histology on the pattern of metastasis and patient survival. All patients with nonmetastatic renal cortical tumors undergoing partial or radical nephrectomy were identified from a renal tumor database between July 1989 and July 2002. Kaplan-Meier and Cox regression tests were used for statistical analysis. Analysis revealed 1057 patients: 794 with conventional clear cell RCC, 157 with papillary RCC, and 106 with chromophobe RCC. Metastasis occurred in 95 conventional clear cell RCC, 9 papillary RCC, and 6 chromophobe RCC with a median follow-up of 34.6, 43.0, and 33.2 months, respectively. Using log-rank analysis, chromophobe and papillary RCC were associated with an improved disease-free survival at 5 years (P =.009 and.015, respectively). Multivariate analysis revealed tumor size, stage, and chromophobe histology as significant variables for disease progression. Renal cortical tumors have distinct histological subtypes with varying degrees of metastatic potential. Conventional clear cell RCC, which comprises two thirds of renal cortical tumors presenting with localized disease, has a less favorable outcome when compared with papillary and chromophobe RCC. Controlling for size and stage, chromophobe, and not papillary, RCC was a significant variable for disease progression compared with conventional clear cell RCC. Knowledge of renal cortical tumor histological subtype is critical for projecting prognosis, tailoring follow-up strategies, and designing clinical trials.

The Chromophobe Tumor Grading System is the Preferred Grading Scheme for Chromophobe Renal Cell Carcinoma

Objective To analyze the clinicopathological features and prognostic factors of common subtypes of non-transparent renal cell carcinoma. Methods Retrospective analysis of 115 patients with pathologically confirmed non-transparent renal cell carcinoma from January 2003 to December 2017, including 67 males and 48 females, with a male to female ratio of 1.4∶1. The average age is (51.2±13.4) years old. 71 cases were asymptomatic renal cancer, 44 cases had clinical symptoms, including 10 cases of gross hematuria, 28 cases of low back pain, 4 cases of hematuria with low back pain, and 2 cases of abdominal mass. There were 49 open surgery and 66 laparoscopic surgery. 58 patients underwent radical nephrectomy and 57 underwent partial nephrectomy. Of the 115 patients, 17 (14.9%) had abnormal hemoglobin (Hb), 22 (19.1%) had abnormal platelet (PLT) count, 18 (15.7%) had abnormal alkaline phosphatase, and abnormal lactate dehydrogenase 16 cases (13.9%). The Kaplan-Meier survival analysis method was used to calculate the survival rate of patients, and the Cox proportional regression risk model was used to analyze the prognostic factors. Results The postoperative pathological stage was 57 cases in T1a stage, 38 cases in T1b stage, 12 cases in T2a stage, 8 cases in T2b stage, 2 cases of regional lymph node positive, and 113 cases negative; no distant metastasis. Pathological types: 42 cases of renal chromophobe cell carcinoma, 37 cases of papillary renal cell carcinoma type Ⅰ, 36 cases of type Ⅱ. The average follow-up time was 38.6 months, and the rate of loss of follow-up was 3.5% (4/115). The 1, 3, and 5 year overall survival rates of 115 patients with common subtypes of non-transparent renal cell carcinoma were 99.1%, 95.8%, and 81.1%, respectively. Multivariate Cox regression analysis found that the pathological type (OR=4.625, P=0.014), four indicators ≥3 abnormalities (OR=30.853, P=0.024), lymph node metastasis (OR=35.663, P=0.006) were the group. An independent factor in the survival time of patients with common subtypes of non-transparent renal cell carcinoma. Conclusions Compared with papillary renal cell carcinoma type Ⅰ and renal chromophobe cell carcinoma, papillary renal cell carcinoma type Ⅱ has a higher degree of malignancy and a poor prognosis. The pathological types of the common subtypes of non-transparent renal cell carcinoma, four indicators (Hb, PLT count, alkaline phosphatase, and lactate dehydrogenase)≥3 abnormalities and lymph node metastasis are independent prognostic factors for overall survival. Key words: Non-transparent renal cell carcinoma; Renal chromophobe cell carcinoma; Papillary renal cell carcinoma; Prognosis

Objectives To improve the diagnosis level of renal chromophobe cell carcinoma(RCCC) and the recognition of renal cell carcinoma(RCC). Methods The clinical data of 21 patients with RCCC (11 men and 10 women) were analyzed. Their age ranged from 27 to 85 years, with a mean of 52 years. 11 cases underwent retroperitoneal laparoscopic radical nephrectomy, 8 cases underwent laparoscopic partial nephrectomy and 2 cases underwent open radical nephrectomy. Results Postoperative pathological findings confirmed the diagnosis of RCCC. The pathologic TNM stage of RCCC was as follows: pT1N0M0 in 13 cases, pT2N0M0 in 5 cases, pT3aN1M0 in 2 cases and pT4N0M0 in 1 case.The Furhman pathologic grade of RCCC was G1 in 6 cases, G2 in 14 cases and G3 in 1 case. Nineteenth cases were followed up. During the follow-up of 3 to 36 months(mean 17 months). One case died of heart attack, one case had local recurrence and died of pulmonary infection, one case died of pulmonary metastasis of carcinoma and 16 cases were surviving tumor free. Conclusions RCCC is a morphologically distinctive uncommon type of RCC. Radical nephrectomy is the first choice for the treatment of RCCC. Compared with other types of RCC at the same stage and of the same grade, RCCC has a better prognosis. Key words: Kidney Neoplasms; Prognosis

e21088 Background: Notch genes play a critical role in growth, development and tumorigenesis. HIF1-α can interact with the Notch intracellular domain to augment the Notch downstream response. Because the Notch signalling pathway is responsive to hypoxia we examined, in this study, the patterns of expression and clinical significance of Notch, Notch receptors and Hif1-α and β in human renal cell carcinoma paraffin-embedded tissues. Methods: Eighty cases of renal cell carcinoma (RCC) tissues were detected by immunohistochemistry. RNA of quality only was obtained in 60 samples (80% clear RCC, 10% papillary RCC and 10% chromophobe RCC) to carry out the study of gene expression through qPCR (quantitative real-time polymerase chain reaction). A pool of normal kidney-derived RNA samples (N=5) was used as healthy control. GAPDH and YWHAZ were used as reference genes. GenEx software was used for qPCR data processing and analysis. Results: Mann-Whitney's U test nonparametric statistical analysis showed: Hif1- α, Hif1- β, Notch1 and Notch3 were upregulated in chromophobe RCC (p=0.045, p=0.03, p=0.03 and p=0.02 respectively). Hif1- α and Notch3 were upregulated in clear RCC (p=0.034 and p=0.041 respectively). Spearman's correlation coefficient showed a strong positive correlation between Nocth1-4 members and their receptors and Hif1-α and β genes. Highlight the correlation found between: Notch1 and Hif1-α (Spearman's rho = 0.740, significance level 0.01) and Hif1-β and Jagged1 (Spearman's rho = 0.752, significance level 0.01). Conclusions: Our findings indicated that the co-expression of Notch receptors, their ligands and Hif-1 α and Hif1- β subunits may play a role in human RCC. Notch cascade may represent a novel and therapeutically accessible pathway in chromophobe and clear RCC. More detailed studies of these crossing pathways should be continued in the future.

Objective To analyze the prognostic factors of adult nonclear cell renal cell carcinoma (nccRCC). Methods The clinical data of 286 patients with pathologically diagnosed one specific type of nccRCC after radical nephrectomy and nephron sparing surgery(NSS) in the affiliated hospital of Qingdao university followed up from January 2012 to January 2019 were retrospectively analyzed.There were 159 males and 127 females. Their age ranged from 17 to 81 years old, with an average age of 53. Based on the AJCC combination stage, 218 cases were in stage Ⅰ, 56 cases were in stage Ⅱ, 9 cases were in stage Ⅲ, 3 cases were in stage Ⅳ. Assay indicators were collected, including lymphocyte percentage(LY%)(31.5±10.5), neutrophil-lymphocyte ratio(NLR)(2.6±2.8), albumin(40.9±4.7)g/L, prealbumin(255.0±74.3)mg/L, lactate dehydrogenase (LDH)(201.0±174.0)U/L, creatine kinase isoenzyme (CK-MB)(20.0±62.1)U/L, total cholesterol(4.9±1.0)mmol/L, blood urea nitrogen/creatinine (BUN/Cr)(12.9±9.9), blood glucose(5.4±1.3)mmol/L, triglyceride(1.4±1.1)mmol/L, low-density lipoprotein cholesterol (LDL-C)(2.9±0.8)mmol/L. The optimal cut-off value of the above indexes were obtained by the receiver operating characteristic curve(ROC) in the SPSS software, and difference between high cut-off and low cut-off divided basing on the optimal cut-off value were evaluated respectively. The prognostic factors of adult nccRCC were evaluated by univariate and multivariate Cox proportional hazards regression analysis. Kaplan-Meier survival curve was used to study the survival relationship. The log-rank test were used to compare survival rate in two groups. The prognostic factors of nccRCC were analyzed after the results above were presented. Prognostic factors in renal chromophobe cell carcinoma and papillary cell carcinoma were analyzed by the same method. Results The 286patients were followed up from 1 to 87 months, with an average of 43.9 months. The 3-year and 5-year survival rates were 93.8% and 89.3%, respectively. Results of univariate and multivariate Cox regression model revealed that AJCC combined staging (HR=2.38, 95%CI1.48-3.83), LDH(HR=2.99, 95%CI1.16-7.69), blood glucose (HR=4.13, 95%CI 1.74-9.78), CK-MB (HR=3.85, 95%CI1.63-9.08) were independent prognostic factors of nccRCC. NLR(HR=8.28, 95%CI1.66-41.35) and LDH(HR=9.82, 95%CI2.94-32.82) were the independent prognostic factor in the renal chromophobe cell carcinoma subgroup and the papillary renal cell carcinoma subgroup, separately. Conclusions AJCC combination stage, LDH, blood glucose and CK-MB are independent prognostic factors of adult nccRCC. Patients with low LDH, hypoglycemia, CK-MB and early AJCC stage have better prognosis. NLR is an independent predictor of renal chromophobe cell carcinoma, and the low NLR group has a better prognosis and higher survival rate. LDH is an independent predictor of papillary renal cell carcinoma and low LDH is beneficial to patients' prognosis. NLR and LDH can be used as a prognostic indicator for clinical evaluation in renal chromophobe cell carcinoma and papillary renal cell carcinoma, respectively. Key words: Kidney neoplasms; Nonclear cell renal cell carcinoma; Pathology; Prognosis