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Introduction : Recently increasing evidence has suggested that obesity is associated with the development and prognosis of renal cell carcinoma. The aim of the study was to investigate the association between different obesity measurements and overall survival in patients with surgically treated clear cell renal cell carcinoma. Patients and Methods : The data of 342 consecutive patients who underwent radical or partial nephrectomy at Peking University People's Hospital from January 2009 to November 2014 were retrospectively reviewed. Median follow-up was 82 months. The association between different obesity measurements and overall survival was evaluated using the Kaplan-Meier method and Cox regression models. Results : In univariate Cox regression analyses, perirenal fat accumulation was significantly associated with overall survival (HR: 2.271; 95%CI: 1.311-3.935; p=0.003), as well as age, sex, clinical manifestation, surgical option, tumor size and grade. The other obesity measurements, including body mass index, waist circumference, total adipose tissue, visceral adipose tissue and percentage of visceral adipose tissue, were not assessed as prognostic indicators of overall survival in this study (p>0.05). After adjusting for age, sex, clinical manifestation, surgical option, tumor size, T stage and tumor grade, perirenal fat accumulation was still identified as an independent predictor of overall survival (HR: 2.264; 95%CI: 1.305-3.926; p=0.004). The results of Kaplan-Meier model also revealing that patients with higher percentage of perirenal fat showed poorer overall survival (p=0.003). Conclusion : Higher percentage of perirenal adipose tissue is independently associated with increased mortality risk in surgically treated clear cell renal cell carcinoma. MicroAbstract : The association between obesity and the prognosis of ccRCC patients is conflicting. Herein we conducted this study to examine the association between different obesity measurements and overall survival in patients with surgically treated ccRCC. In total, 342 patients with ccRCC were enrolled. The results indicate that the percentage of perirenal adipose tissue is superior to both BMI and percentage of visceral fat surface area for predicting overall survival.

Background Intratumoral fibrosis was positively correlated with histological grade of renal clear cell carcinoma (ccRCC) and intratumoral inflammation. However, the association of intratumoral fibrosis with the immune infiltration of ccRCC was few evaluated. Methods We used the second harmonic generation (SHG)-based imaging technology and evaluated the intratumoral fibrosis in ccRCC, and then divided the patients into the high fibrosis group (HF) and the low fibrosis group (LF). Meanwhile, the Kaplan–Meier survival curve analysis was performed to analyze the relationship between intratumoral fibrosis and the disease-free survival rate. Antibody arrays were used for seeking difference in cytokines and immune infiltration between the HF group (N = 11) and LF group (N = 11). The selected immune infiltration marker was then verified by immunohistochemistry (IHC) staining in 45 ccRCC samples. Results Out of 640 cytokines and immune infiltration markers, we identified 115 proteins that were significantly different in quantity between ccRCC and adjacent normal tissues. In addition, the Venn diagram indicated that six proteins, including Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), were significantly associated with intratumoral fibrosis (p p Conclusions The study indicated that the intratumoral fibrosis level was negatively correlated with the expression of CTLA4 in the tumor immune microenvironment of the ccRCC, which posed the potential value of targeting the stroma of the tumor, a supplement to immunotherapy. However, the specific mechanism of this association is still unclear and needs further investigation.

Background The involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues. Methods The phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated. Results The phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase. Conclusion Selective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0525-1) contains supplementary material, which is available to authorized users.

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

To elucidate the glycoprotein non-metastatic melanoma protein B(Gpnmb) expression in clear-cell renal cell carcinoma (ccRCC) and to determine its potential prognostic relevance.A total of 12 pairs of ccRCC tissue specimens were collected from patients undergoing surgery in our hospital from March 2009 to March 2012. Gpnmb expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for another 43 evaluable patients.The expression level of Gpnmb was significantly higher in metastatic ccRCCs than that in matched primary samples ((6.36±4.01) vs (3.14±2.38) scores, P=0.036). The high expression of Gpnmb was not affected by age, gender, clinical stage and pathological grade (all P0.05). Kaplan-Meier analysis disclosed significant differences in overall survival for patients with higher and lower average Gpnmb expression levels (P=0.020). Cox regression analysis revealed that a high Gpnmb protein expression level in the tumor cell could be identified as an independent poor prognostic marker of overall survival in ccRCC patients (P=0.049).Over expression of Gpnmb in tumour cell predicts a poor prognosis of patients with ccRCC.

It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues. Importantly, functional transcripts of IgG with unique VHDJH rearrangement patterns were also found in bladder cancer cells. The knockdown of IgG in bladder cancer cell lines using small interfering RNA significantly inhibited the proliferation, migration and invasion of the cells. Notably, high IgG expression, as determined by immunostaining, was significantly correlated with a high histological grade and recurrence. The results of the present study suggested that IgG expression is involved in the malignant biological behavior and poor prognosis of bladder cancer. Therefore, IgG may serve as a novel target for bladder cancer therapy.

Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.

Current cancer therapies are largely reliant upon drugs and radiation that kill dividing cells or inhibit cell division in the primary tumor after radical surgery, whereas metastatic tumors should be more commonly the focus of targeted molecular therapies. Glycoprotein non‑metastatic melanoma protein B (Gpnmb) is expressed in various types of cancer, and promotes the migration, invasion and metastasis of tumor cells. Thus, it was hypothesized that a unique clear‑cell renal carcinoma (ccRCC) subclone expressing a high level of Gpnmb may metastasize more easily and thus be associated with poor prognosis. In the present study, the expression of Gpnmb was analyzed in primary and metastatic ccRCC samples, and the expression levels of Gpnmb were significantly higher in metastatic ccRCCs than in matched primary samples (P=0.036). Receiver operating characteristic (ROC) curve analysis was then performed to determine a cutoff score for Gpnmb expression in another 43 primary ccRCCs. For validation, the ROC‑derived cutoff score was subjected to an analysis of the association between Gpnmb expression and patient outcome/clinical characteristics. Kaplan‑Meier analysis demonstrated that elevated Gpnmb expression predicted a poorer overall survival (OS) in 43 cases of primary ccRCC. In addition, multivariate analyses revealed that Gpnmb expression served as an independent risk factor for ccRCC. Thus, the overexpression of Gpnmb identified patients at high risk and Gpnmb is a potential therapeutic molecular target for this type of tumor.