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Abstract To analyze the expression levels, prognostic value and immune infiltration association of Holliday junction protein (HJURP) as well as its feasibility as a pan-cancer biomarker for different cancers. The Protter online tool was utilized to obtain the localization of HJURP, then the methylation of HJURP in tumors were further explored. Thereafter, the mRNA data and clinical characteristics of 33 tumor types from TCGA database were obtained to investigate the expression and prognostic relationship of HJURP in different tumor types. Finally, the composition pattern and immune infiltration of HJURP in different tumors were detected in Tumor Immune Estimation Resource. HJURP was abnormally expressed in most of the cancer types and subtypes in TCGA database. Also, it was associated with poor prognosis of different cohorts. At the same time, the results also showed that HJURP was related to tumor immune evasion through different mechanisms, including T cell rejection and methylation in different cancer types. Besides, the methylation of HJURP was inversely proportional to mRNA expression levels, which mediated the dysfunctional phenotypes of T cells and poor prognosis of different cancer types. Alternatively, our results indicated that HJURP expression was associated with immune cell infiltration in a variety of cancers. HJURP may serve as an oncogenic molecule, and its expression and immune infiltration characteristics can be used as a biomarker for cancer detection, prognosis, treatment design and follow-up.

Abstract Objective This work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC). Methods We obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan–Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation. Results CENPA expression enhanced in PRCC tissues compared with healthy counterparts (P

ObjectiveVariants in the glucocerebrosidase (GBA) gene are the most common and significant risk factor for Parkinson’s disease (PD). However, the impact of GBA variants on PD disease progression in the Chinese population remains unclear. This study aimed to explore the significance of GBA status on motor and cognitive impairment in a longitudinal cohort of Chinese patients with PD.MethodsThe entire GBA gene was screened by long-range polymerase chain reaction (LR-PCR) and next generation sequencing (NGS). A total of 43 GBA-related PD (GBA-PD) and 246 non-GBA-mutated PD (NM-PD) patients with complete clinical data at baseline and at least one follow-up were recruited for this study. The associations of GBA genotype with rate of motor and cognitive decline, as measured by Unified PD Rating Scale (UPDRS) motor and Montreal Cognitive Assessment (MoCA), were assessed by linear mixed-effect models.ResultsThe estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [−0.53 (0.11) points/year] progression rates in the GBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); −0.29 (0.04) points/year; respectively]. In addition, the GBA-PD group showed significantly faster estimated (SE) bradykinesia [1.04 (0.18) points/year], axial impairment [0.38 (0.07) points/year], and visuospatial/executive [−0.15 (0.03) points/year] progression rates than the NM-PD group [0.62 (0.10); 0.17 (0.04); −0.07 (0.01) points/year; respectively].ConclusionGBA-PD is associated with faster motor and cognitive decline, specifically greater disability in terms of bradykinesia, axial impairment, and visuospatial/executive function. Better understanding of GBA-PD progression may help predict prognosis and improve clinical trial design.

Objective: Adrenocortical carcinoma (ACC) is a rare malignant tumor. Chromatin regulators (CRs) can drive epigenetic changes, which have been considered as one of the most vital hallmarks of tumors. This study aimed to explore the CR signature for ACC in order to clarify the molecular basis of ACC’s pathogenic mechanism and provide novel methods to diagnose and treat ACC clinically.Methods: This study obtained transcriptome sequencing datasets of ACC patients and sequencing data on normal adrenal tissues in TCGA and GTEx databases, respectively. Meanwhile, prognostic genes were selected through Lasso and Cox regression analyses. Using the transcriptome sequencing datasets of ACC patients downloaded from the GEO database to finish validation, we performed Kaplan–Meier (KM) analysis for evaluating the differential survival between low- and high-risk groups. Then, this work constructed the risk model for predicting ACC prognosis. TIMER 2.0 was employed to assess the differences in immune infiltration between the two groups. Furthermore, this work adopted the R package “pRRophetic” for exploring and estimating the sensitivity of patients to different chemotherapeutic agents.Results: A 5-CR model was established to predict ACC survival, and the CR signature was confirmed as a factor in order to independently predict ACC patient prognosis. In addition, a nomogram composed of the risk score and clinical T stage performed well in the prediction of patients’ prognosis. Differentially expressed CRs (DECRs) were mostly associated with the cell cycle, base excision repair, colon cancer, gene duplication, homologous recombination, and other signaling pathways for the high-risk group. As for the low-risk group, DECRs were mainly enriched in allograft rejection, drug metabolism of cytochrome P450, metabolism of xenogeneic organisms by cytochrome P450, retinol metabolism, and other signaling pathways. According to TIMER analysis, the immune infiltration degrees of endothelial cells, M2 macrophages, myeloid dendritic cells, CD4+ Th1 cells, NKT cells, and M0 macrophages showed significant statistical differences between the high- and low-risk groups, and high infiltration levels of M0 and M2 macrophages were more pronounced in higher T stage (T3 and T4), N stage (N1), and clinical stages (III and IV). In addition, high-risk cases exhibited higher sensitivity to etoposide and doxorubicin. Additionally, low-risk patients had significantly decreased expression of RRM1 compared with high-risk cases, suggesting the better effect of mitotane treatment.Conclusion: This study identified the DECRs, which might be related to ACC genesis and progression. The pathways enriched by these DECRs were screened, and these DECRs were verified with excellent significance for estimating ACC survival. Drug sensitivity analysis also supported the current clinical treatment plan. Moreover, this study will provide reliable ideas and evidence for diagnosing and treating ACC in the clinic.

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson’s disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI.Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC).Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115−1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009−1.119, p = 0.016).Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.

BackgroundIncreasing evidence has indicated that abnormal epigenetic factors such as RNA m6A modification, histone modification, DNA methylation, RNA binding proteins and transcription factors are correlated with hepatocarcinogenesis. However, it is unknown how epigenetic modification-associated genes contribute to the occurrence and clinical outcome of hepatocellular carcinoma (HCC). Thus, we constructed the epigenetic modification-associated models that may enhance the diagnosis and prognosis of HCC.MethodsIn this study, we focused on the clinical value of epigenetic modification-associated genes for HCC. Our gene expression data were collected from TCGA and HCC data sets from the GEO database to ensure the reliability of the data. Their functions were analyzed by bioinformatics methods. We used lasso regression, Support vector machine (SVM), logistic regression and Cox regression to construct the diagnostic and prognostic models. We also constructed a nomogram of the practicability of the above-mentioned prognostic model. The above results were verified in an independent liver cancer data set from the ICGC database and clinical samples. Furthermore, we carried out pan-cancer analysis to verify the specificity of the above model and screened a wide range of drug candidates.ResultsMany epigenetic modification-associated genes were significantly different in HCC and normal liver tissues. The gene signatures showed a good ability to predict the occurrence and survival of HCC patients, as verified by DCA and ROC curve analysis.ConclusionGene signatures based on epigenetic modification-associated genes can be used to identify the occurrence and prognosis of liver cancer.

Background: Transmembrane protein 16A (TMEM16A), also known as ANO1 (anoctamin-1), was reported to be vital in the growth and invasion of several malignancies. However, role of TMEM16A in lung cancer remained unclear. The aim of this study was to evaluate the expression of TMEM16A and its significance in lung cancer. Methods: qRT-PCR and Western blots were performed to evaluate the TMEM16A mRNA and protein expression. Proliferation and invasion of H1299 cancer cells were evaluated by CCK-8 and transwell assays. Tumor volumes in nude mice implanted with H1299 cells were assessed once every week for 5 weeks by measuring 2 perpendicular dimensions. Immunofluorescent staining revealed expression of TMEM16A in nude mice cancer tissues. Results: Our findings provided compelling evidence that TMEM16A production in H1299 cells is 2.1 times higher than observations in HBE16 cells. We showed that overexpression of TMEM16A contributed to the proliferation of H1299 cells. Moreover, T16Ainh-A01, a specific TMEM16A inhibitor or shRNA targeting TMEM16A somewhat inhibited lung tumor cell growth and invasion as evident from in vitro studies and from in vivo xenograft-tumor growth. Inhibition of TMEM16A strongly suppressed EGFR phosphorylation and growth of lung cancer cells. Furthermore, a reduction of p-RAS and p-ERK1/2 was also observed. Conclusion: TMEM16A promoted growth and invasion in lung cancer cells via an EGFR/ MAPK-dependent signaling pathway. So we infer TMEM16A membrane protein may have potential to serve as a biomarker in lung cancer. [ABSTRACT FROM AUTHOR]

Adding Sewage Sludge (SS) in sintering process may provide an alternative for disposal of SS. Therefore, the combustion characteristics of SS and Coal Powder (CP) mixed with the sinter were compared by Thermogravimetric Analysis (TGA) and the effects of adding SS on metallurgical properties of sinter were investigated by sintering pot tests in this paper. TGA results show that the combustion characteristics of SS (5%)-Sinter are better than CP (5%)-Sinter at the same heating rate. Besides, it is beneficial to decrease the ignition temperature by adding more SS into the sinter. The results of sintering pot tests indicate that increasing SS from 0% to 9% in the sintering process can increase the tumbler strength from 62% to 68% and the shatter strength from 63% to 67.4%, and reduce the abrasion index from 4.5% to 3.8%. In addition, the S content in the sinter from sintering pot tests, obtained via X-Ray Fluorescence, decreases from 0.223% to 0.197% and the P content increases from 0.201% to 0.276%; however, these changes are acceptable for the sinter. All these imply that SS is not only a good fuel for sintering, but that adding SS in the sintering process is appropriate as it could improve the metallurgical properties of the sinter to some extent. This will provide a good basis for the practical use of SS in the sintering process of the steel plant. [ABSTRACT FROM AUTHOR]

Studies investigating the association between glutathione S-transferase M1 (GSTM1) polymorphism and bladder cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. We performed a systematic search of the National Library of Medline and Embase databases. This meta-analysis included 26 case-control studies, which included 5029 bladder cancer cases and 6680 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of bladder cancer (OR = 1.46, 95% confidence interval [CI] = 1.35, 1.57). When stratifying for race, results were similar among Asians (OR = 1.60, 95% CI = 1.27, 2.01) and Caucasians (OR = 1.44, 95% CI = 1.33, 1.57) except Africans (OR = 1.25, 95% CI = 0.76, 2.06). When stratifying by the smoking, stage, grade, and histological type of bladder cancer, we found no statistical association. Our meta-analysis suggests that the GSTM1 null genotype is associated with a modest increase in the risk of bladder cancer. [ABSTRACT FROM AUTHOR]