Metastatic renal cell carcinoma (MRCC) is one of the malignancies that are sensitive to immunotherapy. However, the underlying immune inhibitory factors such as myeloid-derived suppressor cells (MDSCs) might restrain the efficacy of immunotherapy. The present study investigates the clinical efficacy of cytokine-induced killer (CIK) cell therapy in patients with MRCC and explores whether the levels of peripheral MDSCs are associated with the prognosis of patients receiving this therapy. Twenty-nine patients with measurable MRCC were treated with an adoptive transfer of autologous CIK cells, followed by 5 consecutive days of interleukin-2 administration. The tumor response and 1-year survival were observed. The proportion of MDSCs in the peripheral blood was detected, and the correlation of MDSCs with prognosis was analyzed. Of 29 evaluable patients, no complete responses were seen; 4 patients exhibited a partial response (13.8%), 18 patients displayed stable disease (62.1%), and 7 patients showed progressive disease (24.1%). Twenty patients (69.0%) were alive 14.8-41.4 months at the time of the last follow-up (median follow-up=20.2 mo). The 1-year survival was 82.8% (24/29). Peripheral blood MDSCs were elevated in almost all MRCC patients and decreased after CIK-cell infusion. Subgroup analysis indicated that patients with a relatively low proportion of MDSCs exhibited prolonged survival. In conclusion, our data suggest that transfusion of autologous CIK cells can induce regression of MRCC, and MDSCs can serve as a potential marker for the prognosis of patients receiving a CIK-based therapy.

Elongation factor, RNA polymerase II, 2 (ELL2) is an RNA Pol II elongation factor with functional properties similar to ELL that can interact with the prostate tumor suppressor EAF2. In the prostate, ELL2 is an androgen response gene that is up-regulated in benign prostatic hyperplasia (BPH). We recently showed that ELL2 loss could enhance prostate cancer cell proliferation and migration, and that ELL2 gene expression was down-regulated in high Gleason score prostate cancer specimens. Here, prostate-specific deletion of ELL2 in a mouse model revealed a potential role for ELL2 as a prostate tumor suppressor in vivo. Ell2 knockout mice exhibited prostatic defects including increased epithelial proliferation, vascularity and PIN lesions similar to the previously determined prostate phenotype in Eaf2 knockout mice. Microarray analysis of prostates from Ell2 knockout and wild-type mice on a C57BL/6J background at age 3 mos and qPCR validation at 17 mos of age revealed a number of differentially expressed genes associated with proliferation, cellular motility and epithelial and neural differentiation. OncoPrint analysis identified combined down-regulation or deletion in prostate adenocarcinoma cases from the Cancer Genome Atlas (TCGA) data portal. These results suggest that ELL2 and its pathway genes likely play an important role in the development and progression of prostate cancer.

Objective. Osteoarthritis (OA) is a complex arthritic condition in which the genetic factor plays a major role. One of the candidate genes of is the ADAM12 gene, but no consistency has been reached till now. This study aims to investigate the potential role of four single nucleotide polymorphisms (SNPs) of the ADAM12 gene in susceptibility to knee OA and its progression in Chinese Han population. Methods. The rs1278279, rs3740199, rs1044122, and rs1871054 polymorphisms were genotyped and compared in a population based cohort consisting of 164 OA subjects and 200 age- and gender-matched controls. Results. The SNP rs1871054 was found with increased risk of OA susceptibility in comparing the genotype frequencies between the case and control groups no matter for which model of comparison (allele level, dominant model, recessive model, and extreme genotype model). Additionally, the SNP rs1871054 was found associated with increased OA severity according to the K/L grade. Conclusion. In summary, we have identified that the rs1871054 variant within the ADAM12 gene is a risk factor for increased osteoarthritis susceptibility and severity.

BackgroundAdvanced pancreatic cancer (PC) has very poor prognosis with present treatments, thus necessitating continued efforts to find improved therapeutic approaches. Both preclinical and preliminary clinical data indicate that cytokine-induced killer (CIK) cells are an effective tool against various types of solid tumors. Here, we conducted a study to determine whether CIK cell-based therapy (CBT) can improve the outcomes of advanced PC.MethodsEighty-two patients with advanced PC, whose predicted survival time was longer than 3 months, were analyzed retrospectively. Of all the patients, 57 individuals were receiving chemotherapy, while the remaining 25 individuals were treated with CBT.ResultsThe overall survival analysis was based on 48 deaths in the 57 patients in the chemotherapy group (84.2 %) and 18 deaths in the 25 patients in the CBT group (72.0 %). In the CBT group, the median overall survival time was 13.5 months, as compared to 6.6 months in the chemotherapy group (hazard ratio for death, 0.39; 95 % confidence interval, 0.23 to 0.65; p < 0.001). The survival rate was 88.9 % in the CBT group versus 54.2 % in the chemotherapy group at 6 months, 61.1 % versus 12.5 % at 12 months, and 38.9 % versus 4.2 % at 18 months. The disease control rate was 68.0 % in the CBT group and 29.8 % in the chemotherapy group (p < 0.001).ConclusionsThese results from this retrospective analysis appeared to imply that CBT might prolong survival in these high-risk PC patients. Prospective study is needed to corroborate this observation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0237-6) contains supplementary material, which is available to authorized users.

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Background Renal cell carcinoma (RCC) is a common malignant tumour of the genitourinary system. We aimed to analyse the potential value of metastasis-related biomarkers, circulating tumour cells (CTCs) and the proliferative marker Ki-67 in the diagnosis of RCC. Methods Data from 24 laparoscopic radical nephrectomies (RNs) and 17 laparoscopic partial nephrectomies (PNs) were collected in 2018. The numbers and positive rates of CTCs and circulating tumour microemboli (CTM) in the peripheral blood were obtained at three different time points: just before surgery, immediately after surgery and 1 week after surgery. Ki-67 protein expression was evaluated in the RCC tissue by immunohistochemistry. Results Except for the statistically significant association between the preoperative CTC counts and tumour size, no association between the number and positive rate of perioperative CTCs and clinicopathological features was found. The CTC counts gradually decreased during the perioperative period, and at 1 week after surgery, they were significantly lower than those before surgery. High Ki-67 expression was significantly positively correlated with preoperative CTC counts. In addition, Ki-67 expression was higher in the high CTC group (≥ 5 CTCs). Conclusion Our results suggest that surgical nephrectomy is associated with a decrease in CTC counts in RCC patients. CTCs can act as a potential biomarker for the diagnosis and prognosis of RCC. A careful and sufficient long-term follow-up is needed for patients with high preoperative CTC counts.

Background: Bladder cancer (BLCA) is a common malignant tumor of the genitourinary system, and there is a lack of specific, reliable, and non-invasive tumor biomarker tests for diagnosis and prognosis evaluation. Homeobox genes play a vital role in BLCA tumorigenesis and development, but few studies have focused on the prognostic value of homeobox genes in BLCA. In this study, we aim to develop a prognostic signature associated with the homeobox gene family for BLCA.Methods: The RNA sequencing data, clinical data, and probe annotation files of BLCA patients were downloaded from the Gene Expression Omnibus database and the University of California, Santa Cruz (UCSC), Xena Browser. First, differentially expressed homeobox gene screening between tumor and normal samples was performed using the “limma” and robust rank aggregation (RRA) methods. The mutation data were obtained with the “TCGAmutation” package and visualized with the “maftools” package. Kaplan–Meier curves were plotted with the “survminer” package. Then, a signature was constructed by logistic regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using “clusterProfiler.” Furthermore, the infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, the performance of the signature was evaluated by receiver-operating characteristic (ROC) curve and calibration curve analyses.Results: Six genes were selected to construct this prognostic model: TSHZ3, ZFHX4, ZEB2, MEIS1, ISL1, and HOXC4. We divided the BLCA cohort into high- and low-risk groups based on the median risk score calculated with the novel signature. The overall survival (OS) rate of the high-risk group was significantly lower than that of the low-risk group. The infiltration levels of almost all immune cells were significantly higher in the high-risk group than in the low-risk group. The average risk score for the group that responded to immunotherapy was significantly lower than that of the group that did not.Conclusion: We constructed a risk prediction signature with six homeobox genes, which showed good accuracy and consistency in predicting the patient’s prognosis and response to immunotherapy. Therefore, this signature can be a potential biomarker and treatment target for BLCA patients.

BackgroundRheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA.MethodsThe integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein–protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA. In addition, the expression level of identified candidate DEGs was preliminarily detected in peripheral blood cells of RA patients in the dataset. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression levels of identified DEGs in RA.ResultsA total of 378 DEGs, including 202 up- and 176 down-regulated genes, were identified in synovial tissues of RA patients compared with healthy controls. DEGs were significantly enriched in axon guidance, RNA transport and MAPK signaling pathway. RBFOX2, LCK and SERBP1 were the hub proteins in the PPI network. In the TF-target gene network, RBFOX2, POU6F1, WIPF1 and PFKFB3 had the high connectivity with TFs. The expression status of 11 candidate DEGs was detected in , the expression levels of MAT2A and NSA2 were significantly down-regulated and CD47 had the up-regulated tendency in peripheral blood cells of patients with RA compared with healthy individuals. qRT-PCR results of MAT2A, NSA2, CD47 were compatible with our bioinformatics analyses.DiscussionOur study might provide valuable information for exploring the pathogenesis mechanism of RA and identifying the potential biomarkers for RA diagnosis.