FLOT-2 is an independent prognostic marker in oral squamous cell carcinoma

Flotillin-2 (Flot-2) is an important component of cellular membrane, which involves in various cellular processes and recent studies have revealed that Flot-2 played important roles in cancer progression. The expression and prognostic impact of Flot-2 in oral squamous cell carcinoma (OSCC) have not been well studied. So, a tissue microarray (TMA) based on immunohistochemical analysis of surgical resection of tumor tissues of 78 cases of OSCC patients and 27 cases of adjacent non-cancerous squamous epithelium tissues was conducted. This study focused on detecting Flot-2 expression and analyzing its prognostic impact on OSCC. The result showed that the positive percentage of Flot-2 expression in OSCC (74.4%, 58/78) was significantly higher than that in adjacent non-cancerous squamous epithelium tissues (25.9%, 7/27) (P<0.001). Additionally, the positive expression of Flot-2 in OSCC patients with a history of alcohol consumption was significantly higher than those nonusers (P=0.027). Both univariate and multivariate survival analysis indicated that increased expression Flot-2 protein was significantly correlated inversely with overall survival rates in OSCC patients (P=0.046, P=0.002). Taken together, positive expression of Flot-2 protein may be an independent biomarker for poor prognosis in OSCC.     

肾癌患者血清中miR-126的异常表达及其临床意义

目的：检测miR-126在肾癌病人血清中的表达状况,同时研究miR-126与肾癌患者临床病理特征之间的关联,为进一步的深入研究奠定基础。方法：收集35例新诊断肾癌患者术前血清样本,另外收集35例健康体检者血清样本作为对照,利用实时荧光定量PCR技术检测miR-126在肾癌患者血清中的表达情况,利用SPSS19.0软件分析肾癌病人临床病理特征和miR-126表达量两者之间的关系。结果：与对照组比较,肾癌组患者血清中miR-126表达量明显低于健康体检组,差异具有统计学意义(P<0.05),在35例肾癌血清样本中,出现31例miR-126下调(88.57%),而4例则表现为上调(11.43%)。肾癌病人的性别、年龄、肾癌组织类型、肾肿瘤大小、TNM分期和肾癌患者血清中miR-126表达量无相关性(P>0.05)。结论：miR-126在肾癌患者血清中低表达,提示其可能与肾癌的发生和发展相关。     

XIAP expression is an independent prognostic marker in clear-cell renal carcinomas

Deregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. XIAP is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. To explore the relevance of XIAP for progression and prognosis in renal cell carcinomas (RCCs) of the clear-cell type, we analyzed XIAP protein expression in formalin-fixed tissue from 145 clear-cell RCCs by immunohistochemistry. XIAP protein expression was found in 95% of clear-cell RCCs. A significant increase of XIAP expression became evident from well (G1) to poorly (G3) differentiated clear-cell RCCs (P < 0.0001) and from low (pT1) to advanced (pT3) tumor stages (P = 0.0016). Log-rank test showed a significant inverse correlation (P = 0.0174) between XIAP expression and tumor aggressiveness as indicated by patients' survival. Most important, multivariate Cox regression analysis revealed that XIAP expression is an independent prognostic parameter (P = 0.018) in clear-cell RCCs. Our results suggest an important role for XIAP-mediated inhibition of apoptosis during progression of clear-cell RCCs and introduce XIAP expression as a new independent prognostic marker in this tumor type.     

Increased expression of metastasis-associated in colon cancer-1 in renal cell carcinoma is associated with poor prognosis

Metastasis-associated in colon cancer-1 (MACC1) expression in tumor specimens is an independent prognostic indicator of metastasis, which has recently gained considerable attention in cancer research, due to its overexpression in several types of carcinoma. However, MACC1 expression patterns and its possible role in renal cell carcinoma remain unknown. This study aimed to investigate MACC1 expression in renal cell carcinoma via immunohistochemical analysis and determine the relationship between MACC1 expression and cancer prognosis. Positive MACC1 expression was found to significantly correlate with distant metastasis and TNM stage (P < 0.05). A Kaplan-Meier survival analysis revealed that patients with higher MACC1 expression had a significantly lower disease-free rate (P < 0.05). These results indicate that MACC1 expression is significantly associated with prognosis in patients with renal cell carcinoma. To the best of our knowledge, this is the first study on the significance of MACC1 as a prognostic marker in renal cell carcinoma. MACC1 expression may be a useful target for the development of new therapeutic approaches, including molecular targeted therapeutic agents, for renal cell carcinoma.     

Cyclooxygenase-2 expression and relationship to tumour progression in human renal cell carcinoma

AIMS: Cyclooxygenase (COX), which catalyses the synthesis of prostaglandins from arachidonic acid, has two isoforms; COX-1 and COX-2. There is ample evidence to suggest an important role for COX-2 in cancer. The aim of this study was to evaluate the clinical significance of COX-2 expression and its localization in the development and progression of human renal cell carcinoma (RCC). METHODS AND RESULTS: The expression and localization of COX-2 were evaluated in human RCC tissues from 75 patients by immunohistochemistry. Immunoreactive COX-2 protein was observed in all cases of RCC, and the levels of COX-2 expression were correlated with tumour grade and pathological stage. Expression of COX-2 was higher in the granular cell subtype than in the clear cell subtype of RCC. Immunoelectron microscopy revealed that COX-2 was expressed in the nuclear membrane, rough endoplasmic reticulum, Golgi complex and mitochondrial membrane of RCC cells. CONCLUSION: COX-2 overexpression within these intracellular organelles in RCC may be associated with renal cell carcinogenesis and COX-2 may be a useful biomarker in RCC.     

肾黏液样小管状和梭形细胞癌与乳头状肾细胞癌的免疫表型及遗传学改变

目的 研究肾脏黏液样小管状和梭形细胞癌(mucinous tubular and spindle cell carcinoma, MTSCC)及乳头状肾细胞癌(papillary renal cell carcinoma, PRCC)的免疫表型及遗传学特征,探讨它们在肿瘤鉴别诊断中的意义.方法 应用免疫组化方法分别检测7例MTSCC及10例PRCC中 vimentin、RCC、CK7、CK19、34βE12、AMACR、CD10及CD117的表达,同时应用荧光原位杂交(fluorescence in situ hybridization, FISH)技术检测两种肿瘤中7号染色体的遗传学改变.结果 (1) vimentin、RCC、CK7、CK19、AMACR、CD117及34βE12在两种肿瘤中的表达均无明显差别;CD10在50% (5/10例)的PRCC中呈阳性表达,而在MTSCC 中均呈阴性反应.(2) FISH结果显示:10例 PRCC均存在7号染色体三倍体,而在MTSCC中未检测到这一遗传学改变.结论 MTSCC是一种罕见的低级别多形性肿瘤,其某些组织学特征及免疫表型与PRCC相似,极易误诊.7号染色体的异常改变对MTSCC和PRCC的鉴别诊断有着十分重要的意义.     

The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma

CEACAM1 acts as a tumour suppressor in various epithelial tumours. On the other hand, de novo expression of CEACAM1 is strongly associated with reduced disease-free survival of melanoma and non-small cell lung carcinoma patients. Since effector functions of natural killer and T cells are inhibited by homophilic CEACAM1 interaction, immune escape could be responsible for the poor prognosis of these patients. Here, we describe CEACAM1 expression in normal kidney, renal adenomas and renal cell carcinomas (RCC) using a novel antibody generated by genetic immunization. In normal kidney, CEACAM1 was found in epithelial cells of proximal tubules and in endothelial cells. In contrast, tumour cells of 30 clear cell, three chromophobic, and two chromophilic RCCs were completely devoid of CEACAM1. Renal adenomas also lacked CEACAM1 expression. Similarly, RCC cell lines CaKi1, CaKi2, A498, and RCC26 exhibited no or low-level CEACAM1 expression. However, CEACAM1 expression was transiently induced in A498 cells upon contact with allogeneic CD8+ T cells, mediated at least in part by interferon-gamma. Furthermore, the majority of tumour-infiltrating T and NK cells expressed CEACAM1 upon stimulation. Thus, transient expression of the tumour suppressor CEACAM1 by tumour cells and subsequent homophilic interaction with CEACAM1 on tumour-infiltrating lymphocytes could represent a novel immune escape mechanism in RCC.     

肾癌中cyclinD1和p27kip1的表达及其意义

目的探讨cyc lin D1、p27k ip1在普通型肾细胞癌(renal cell carc inom a,RCC)发生、发展中的作用。方法用半定量RT-PCR方法检测25例普通型RCC和10例肿瘤远端的正常肾组织中cyc lin D1的mRNA含量,用免疫组化方法检测76例普通型RCC中cyc lin D1和p27k ip1蛋白的表达,并对cyc lin D1、p27k ip1蛋白表达与临床病理参数的关系进行分析。结果普通型RCC中cyc lin D1的mRNA含量0.488±0.399,高于正常对照组0.089±0.066(P<0.01)。cyc lin D1的表达与肿瘤体积大小有关,体积大者cyc lin D1高表达(P<0.05)。普通型RCC中p27k ip1表达低于正常对照组,随着p27k ip1表达的降低,肿瘤的细胞核Fu-hrm an分级、TNM分期增高。结论cyc lin D1高表达和p27k ip1的低表达与普通型RCC的发生有关;p27k ip1的低表达可能促进肿瘤的演进,p27k ip1的表达可作为评价普通型RCC预后的参考指标。     

CD40 expression in renal cell carcinoma is associated with tumor apoptosis,CD8 T cell frequency and patient survival

The co-stimulatory molecule, CD40, is expressed in renal cell carcinoma (RCC) and a variety of inflammatory diseases in the kidney. We investigated the relationship between tumor-associated CD40 expression, immune milieu of the tumor microenvironment, tumor stage and survival of patients with RCC. The expression of CD40, TUNEL and CD8 in human renal cell carcinomas was analyzed by immunohistochemistry performed on tissue samples obtained at the time of surgery. Computer-assisted quantitation of protein expression was used to analyze results in connection with patient survival and tumor stage. We show for the first time that tumor-associated CD40 expression is associated with prolonged survival in RCC patients. Tumor apoptosis (TUNEL) and CD8 immunostaining were also associated with patient survival. No relation was observed between CD40 expression and tumor stage. Our results suggest CD40 may be a prognostic biomarker indicative of prolonged RCC patient survival. Strategies that up-regulate CD40 expression in some RCC patients may thus improve survival, supporting further studies of agonistic CD40 antibodies in RCC.     

DRAM1 plays a tumor suppressor role in clear cell renal cell carcinoma through modulating Akt signaling

BackgroundClear cell renal carcinoma (ccRCC) is one of the most common malignant tumors worldwide. DNA damage-regulated autophagy modulator1 (DRAM1) plays an important roles in apoptosis and tumor progression. However, the role of DRAM1 in ccRCC is still unknown. In our study, we aimed to investigate the effect of DRAM1 in the progression of ccRCC.MethodsThe expression and prognostic information of DRAM1 in ccRCC were obtained by immunohistochemistry staining and bioinformatics database. Cell proliferation, migration, invasion were detected by CCK-8 assay, wound-healing and transwell assays, and the cell apoptosis was examined by tunel assay and flow cytometry analysis. Western blot was used to detect the expression of DRAM1, Bax, Bcl2, Akt, p53,E-cadherin, N-cadherin of ccRCC cells.ResultsDecreased expression of DRAM1 was found in ccRCC tissues, which predicted a shorter survival rate in ccRCC patient. We confirmed that DRAM1 inhibited the proliferation, migration, invasion and epithelial mesenchymal transformation (EMT), while enhanced the apoptosis of ccRCC cells. In addition, the results of inhibition of Akt signaling were consistent with the above. We further proved that DRAM1 over-expression decreased the phosphorylation of Akt signaling, and overexpression of DRAM1 could reverse oncogenic function induced by the over-activating of Akt in ccRCC cells.Conclusionoverexpression of DRAM1 plays a tumor suppressive role in ccRCC through inactivation of Akt and highlights the potential role of DRAM1 as a prognostic biomarker in ccRCC.