Reduced expression of SOCS2 and SOCS6 in hepatocellular carcinoma correlates with aggressive tumor progression and poor prognosis

To investigate the clinical significance of suppressor of cytokine signaling (SOCS)-2 and SOCS6 in human hepatocellular carcinoma (HCC). The expression levels of SOCS2 and SOCS6 mRNA and protein in tumor, para-tumor and normal liver tissues were detected in 106 HCC patients by real-time quantitative RT-PCR (qRT-PCR) and Western blot. According to qRT-PCR and western blot analyses, we first found that both the expression levels of SOCS2 and SOCS6 mRNA and protein in HCC were significantly lower than those in para-tumor (both P < 0.001) and normal liver tissues (both P < 0.001). Then, the correlation analysis showed that both SOCS2 and SOCS6 protein downregulation were significantly correlated with advanced TNM stage (both P < 0.001) and high serum AFP (P = 0.008 and 0.01, respectively). Especially, the reduced expression of SOCS2 more frequently occurred in HCC patients with vascular invasion (P = 0.03), and that of SOCS6 was also associated with tumor recurrence (P = 0.01). Moreover, HCC patients with low expression of SOCS2 and SOCS6 had significantly shorter overall (P = 0.008 and 0.01, respectively) and disease-free survival (both P = 0.01). Furthermore, multivariate analysis showed that both SOCS2 and SOCS6 downregulation were independent prognostic factors of overall (P = 0.01 and 0.03, respectively) and disease-free survival (P = 0.01 and 0.03, respectively) in HCC. Our data demonstrate for the first time that SOCS2 and SOCS6 expression were remarkably reduced in HCC and may be served as potential prognostic markers for patients with this deadly disease.     

Analysis of <Emphasis Type="Italic">Malus</Emphasis><Emphasis Type="Italic">S</Emphasis>-RNase gene diversity based on a comparative study of old and modern apple cultivars and European wild apple

Malus S-RNase genetic diversity was analyzed in Malus × domestica cultivars and compared to European wild apple (Malus sylvestris). Using PCR-based approaches, the S-RNase genotype of 140 M. × domestica cultivars, 196 M. sylvestris trees and 27 M. sylvestris—M. × domestica hybrids was determined. S-RNase allelic richness in M. sylvestris was much higher than in M. × domestica, indicating the negative influence of domestication on S-RNase diversity. Heterogeneity of the S-RNase allelic distribution is much higher in cultivated apple than in wild apple, which shows that breeding leads to strong departure from the expected homogeneity of genes under negative frequency-dependent selection. The majority of the M. × domestica S-alleles has been found in M. sylvestris as well, which points to strong conservation of the S-locus gene structure. Based on the sequence of all different SCAR-fragments, which comprise both the hypervariable PS1 region and the single intron, S-RNase genetic diversity was further explored. It provided some clues to the occurrence of new S-alleles among the multitude of novel S-RNase sequences that have been identified, which were mostly unique for the group of M. sylvestris individuals. The determination of the S-RNase genotypes of old cultivars and M. sylvestris will enable their introduction into new breeding strategies. As M. sylvestris has become an endangered species in Belgium, the knowledge gathered in this study will be an important tool for selecting useful genotypes for a core collection.     

Genetic risk scores to predict the prognosis of chronic heart failure patients in Chinese Han

Chronic heart failure (CHF) has poor prognosis and polygenic heritability, and the genetic risk score (GRS) to predict CHF outcome has not yet been researched comprehensively. In this study, we sought to establish GRS to predict the outcomes of CHF. We re‐analysed the proteomics data of failing human heart and combined them to filter the data of high‐throughput sequencing in 1000 Chinese CHF cohort. Cox hazards models were used based on single nucleotide polymorphisms (SNPs) to estimate the association of GRS with the prognosis of CHF, and to analyse the difference between individual SNPs and tertiles of genetic risk. In the cohort study, GRS encompassing eight SNPs harboured in seven genes were significantly associated with the prognosis of CHF (P = 2.19 × 10^?10 after adjustment). GRS was used in stratifying individuals into significantly different CHF risk, with those in the top tertiles of GRS distribution having HR of 3.68 (95% CI: 2.40‐5.65 P = 2.47 × 10^?10) compared with those in the bottom. We developed GRS and demonstrated its association with first event of heart failure endpoint. GRS might be used to stratify individuals for CHF prognostic risk and to predict the outcomes of genomic screening as a complement to conventional risk and NT‐proBNP.     

Down-regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway

Somatic copy number alterations (CNAs) are a genomic hallmark of cancers. Among them, the chromosome 17p13.1 deletions are recurrent in hepatocellular carcinoma (HCC). Here, utilizing an integrative omics analysis, we screened out a novel tumour suppressor gene within 17p13.1, myosin heavy chain 10 (MYH10). We observed frequent deletions (~38%) and significant down-regulation of MYH10 in primary HCC tissues. Deletion or decreased expression of MYH10 was a potential indicator of poor outcomes in HCC patients. Knockdown of MYH10 significantly promotes HCC cell migration and invasion in vitro, and overexpression of MYH10 exhibits opposite effects. Further, inhibition of MYH10 markedly potentiates HCC metastasis in vivo. We preliminarily elucidated the mechanism by which loss of MYH10 promotes HCC metastasis by facilitating EGFR pathway activation. In conclusion, our study suggests that MYH10, a candidate target gene for 17p13 deletion, acts as a tumour suppressor and may serve as a potential prognostic indicator for HCC patients.     

Prognostic value of polarized macrophages in patients with hepatocellular carcinoma after curative resection

As the most predominant tumour‐infiltrating immune cells, tumour‐associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68‐positive TAMs display dissimilarly polarized programmes comprising CD11c‐positive pro‐inflammatory macrophages (M1) and CD206‐positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c‐positive TAM density (P = 0.005) and low versus high CD206‐positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68‐positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence‐free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c‐positive and CD206‐positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.     

Enhanced anti-tumor activity of interferon-alpha in SOCS1-deficient mice is mediated by CD4<Superscript>+</Superscript> and CD8<Superscript>+</Superscript> T cells

Interferon-alpha (IFN-α) is an immunomodulatory cytokine that is used clinically for the treatment of melanoma in the adjuvant setting. The cellular actions of IFN-α are regulated by the suppressors of cytokine signaling (SOCS) family of proteins. We hypothesized that the anti-tumor activity of exogenous IFN-α would be enhanced in SOCS1-deficient mice. SOCS1-deficient (SOCS1^−/−) or control (SOCS1^+/+) mice on an IFN-γ^−/− C57BL/6 background bearing intraperitoneal (i.p.) JB/MS murine melanoma cells were treated for 30 days with i.p. injections of IFN-A/D or PBS (vehicle). Log-rank Kaplan-Meier survival curves were used to evaluate survival. Tumor-bearing control SOCS1^+/+ mice receiving IFN-A/D had significantly enhanced survival versus PBS–treated mice (P = 0.0048). The anti-tumor effects of IFN-A/D therapy were significantly enhanced in tumor-bearing SOCS1^−/− mice; 75% of these mice survived tumor challenge, whereas PBS-treated SOCS1^−/− mice all died at 13-16 days (P = 0.00038). Antibody (Ab) depletion of CD8⁺ T cells abrogated the anti-tumor effects of IFN-A/D in SOCS1^−/− mice as compared with mice receiving a control antibody (P = 0.0021). CD4⁺ T-cell depletion from SOCS1^−/− mice also inhibited the effects of IFN-A/D (P = 0.0003). IFN-A/D did not alter expression of CD80 or CD86 on splenocytes of SOCS1^+/+ or SOCS1^−/− mice, or the proportion of T regulatory cells or myeloid-derived suppressor cells in SOCS1^+/+ or SOCS1^−/− mice. An analysis of T-cell function did reveal increased proliferation of SOCS1-deficient splenocytes at baseline and in response to mitogenic stimuli. These data suggest that modulation of SOCS1 function in T-cell subsets could enhance the anti-tumor effects of IFN-α in the setting of melanoma.     

PDCD1 gene polymorphisms as regulators of T‐lymphocyte activity in cutaneous melanoma risk and prognosis

This study aimed to evaluate whether PD1.1 (c.‐606G>A), PD1 (c.627 + 252C>T), PD1.5 (c.804C>T), and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects, and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89‐fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 versus 1.28 arbitrary units, p = .03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4⁺ lymphocytes (16.6 versus 12.5%, p = .01; 17.0 versus 13.1%, p = .006). At 60 months of follow‐up, short recurrence‐free survival was seen in patients with PD1.1 AA genotype (33.3 versus 71.8%, p = .03). Patients with PD1.1 AA and PD1.5 CC genotype had 4.21 and 2.62 more chances of presenting relapse and evolving death by disease in Cox analyses, respectively. Our data provide preliminary evidence that abnormalities in regulation of T lymphocyte alter CM risk, clinical aspects, and prognosis.     

Expression of genes encoding the luciferase from Photobacterium leiognathi in Escherichia coli Rosetta (DE3) and its application in NADH detection

Cloning of genes encoding the luciferase from Photobacterium leiognathi YL in Escherichia coli Rosetta (DE3) was performed successfully and the expressed forms of lux AB were purified to homogeneity. Experimental measurements revealed that luciferase from Photobacterium leiognathi YL has good thermal stability and a high residual activity at extreme pH values, which are extremely important for its various ecological, industrial and medical applications. Furthermore, we made a first attempt for quantitative detection of NADH by recombinant E. coli Rosetta (DE3) coupled enzyme system. A good linear relationship between luminescence intensity and NADH with low (1–12 nmol/L) and high (10–500 nmol/L) concentration was observed, whose standard curve was y = 772.97× + 4041.1, R² = 0.9884 and y = 1710× + 4.99 × 10⁵, R² = 0.9727, respectively. Our results demonstrate a high sensitivity of recombinant E. coli coupled enzyme system to NADH on the basis of high soluble expression of recombinant luciferase and continuous and stable expression of some NAD(P)H‐dependent flavin mononucleotide (FMN) reductases.     

Nuclear fast red‐based colorimetric sensors for sensitive and selective detection of Ag ions

The reduction of nuclear fast red (NFR) stain by sodium tetrahydroboron was catalyzed in the presence of silver ions (Ag⁺). The fluorescence properties of reduced NFR differed from that of NFR. The product showed fluorescence emission at 480 nm with excitation at 369 nm. Furthermore, the fluorescence intensity of the mixture increased strongly in the presence of Ag⁺ and Britton–Robinson buffer at pH 4.78. There was a good linear relationship between increased fluorescence intensity (ΔI) and Ag⁺ concentration in the range 5.0 × 10^?9 to 5.0 × 10^?8 M. The correlation coefficient was 0.998, and the detection limit (3σ/k) was 1.5 × 10^?9 M. The colour of the reaction system changed with variation in Ag⁺ concentration over a wide range. Based on the colour change, a visual semiquantitative detection method for recognition and sensing of Ag⁺ was developed for the range 1.0 × 10^?8 to 5.0 × 10^?4 M, with an indicator that was visible to the naked eye. Therefore, a sensitive, simple method for determination of Ag⁺ was developed. Optimum conditions for Ag⁺ detection, the effect of other ions and the analytical application of Ag⁺ detection of synthesized sample were investigated.     

CpG‐related SNPs in the MS4A region have a dose‐dependent effect on risk of late–onset Alzheimer disease

CpG‐related single nucleotide polymorphisms (CGS) have the potential to perturb DNA methylation; however, their effects on Alzheimer disease (AD) risk have not been evaluated systematically. We conducted a genome‐wide association study using a sliding‐window approach to measure the combined effects of CGSes on AD risk in a discovery sample of 24 European ancestry cohorts (12,181 cases, 12,601 controls) from the Alzheimer's Disease Genetics Consortium (ADGC) and replication sample of seven European ancestry cohorts (7,554 cases, 27,382 controls) from the International Genomics of Alzheimer's Project (IGAP). The potential functional relevance of significant associations was evaluated by analysis of methylation and expression levels in brain tissue of the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP), and in whole blood of Framingham Heart Study participants (FHS). Genome‐wide significant (p < 5 × 10^?8) associations were identified with 171 1.0 kb‐length windows spanning 932 kb in the APOE region (top p < 2.2 × 10^?308), five windows at BIN1 (top p = 1.3 × 10^?13), two windows at MS4A6A (top p = 2.7 × 10^?10), two windows near MS4A4A (top p = 6.4 × 10^?10), and one window at PICALM (p = 6.3 × 10^‐9). The total number of CGS‐derived CpG dinucleotides in the window near MS4A4A was associated with AD risk (p = 2.67 × 10^?10), brain DNA methylation (p = 2.15 × 10^?10), and gene expression in brain (p = 0.03) and blood (p = 2.53 × 10^?4). Pathway analysis of the genes responsive to changes in the methylation quantitative trait locus signal at MS4A4A (cg14750746) showed an enrichment of methyltransferase functions. We confirm the importance of CGS in AD and the potential for creating a functional CpG dosage‐derived genetic score to predict AD risk.     

Deoxyribonuclease 1-like 3 Inhibits Hepatocellular Carcinoma Progression by Inducing Apoptosis and Reprogramming Glucose Metabolism

HCC has remained one of the challenging cancers to treat, owing to the paucity of drugs targeting the critical survival pathways. Considering the cancer cells are deficient in DNase activity, the increase of an autonomous apoptisis endonuclease should be a reasonable choice for cancer treatment. In this study, we investigated whether DNASE1L3, an endonuclease implicated in apoptosis, could inhibit the progress of HCC. We found DNASE1L3 was down-regulated in HCC tissues, whereas its high expression was positively associated with the favorable prognosis of patients with HCC. Besides, serum DNASE1L3 levels were lower in HCC patients than in healthy individuals. Functionally, we found that DNASE1L3 inhibited the proliferation of tumor cells by inducing G0/G1 cell cycle arrest and cell apoptosis in vitro. Additionally, DNASE1L3 overexpression suppressed tumor growth in vivo. Furthermore, we found that DNASE1L3 overexpression weakened glycolysis in HCC cells and tissues via inactivating the rate-limiting enzymes involved in PTPN2-HK2 and CEBPβ-p53-PFK1 pathways. Finally, we identified the HBx to inhibit DNASE1L3 expression by up-regulating the expression of ZNF384. Collectively, our findings demonstrated that DNASE1L3 could inhibit the HCC progression through inducing cell apoptosis and weakening glycolysis. We believe DNASE1L3 could be considered as a promising prognostic biomarker and therapeutic target for HCC.     

Molecular characterization of circulating tumour cells identifies predictive markers for outcome in primary,triple‐negative breast cancer patients

mRNA profiles of circulating tumour cells (CTCs) were analysed in patients with triple‐negative breast cancer (TNBC) (pts) before (BT) and after therapy (AT) to identify additional treatment options. 2 × 5 mL blood of 51 TNBC pts and 24 non‐TNBC pts (HR+/HER2?; HR?/HER2+) was analysed for CTCs using the AdnaTest EMT‐2/Stem Cell Select?, followed by mRNA isolation and cDNA analysis for 17 genes by qPCR PIK3CA, AKT2, MTOR and the resistance marker AURKA and ERCC1 were predominantly expressed in all breast cancer subtypes, the latter ones especially AT. In TNBC pts, ERBB3, EGFR, SRC, NOTCH, ALK and AR were uniquely present and ERBB2+/ERBB3 + CTCs were found BT and AT in about 20% of cases. EGFR+/ERBB2+/ERBB3 + CTCs BT and ERBB2+/ERBB3 + CTCs AT significantly correlated with a shorter progression‐free survival (PFS; P = 0.01 and P = 0.02). Platinum‐based therapy resulted in a reduced PFS (P = 0.02) and an induction of PIK3CA expression in CTCs AT. In non‐TNBC pts, BT, the expression pattern in CTCs was similar. AURKA+/ERCC1 + CTCs were found in 40% of HR?/HER2 + pts BT and AT. In the latter group, NOTCH, PARP1 and SRC1 were only present AT and ERBB2 + CTCs completely disappeared AT. These findings might help to predict personalized therapy for TNBC pts in the future.     

Effects of water temperature and initial weight on growth,digestion and energy budget of yellow catfish Pelteobagrus fulvidraco (Richardson, 1846)

The effects of water temperature and body weight on feeding, growth, and energy budget were inevitable in the yellow catfish Pelteobagrus fulvidraco (Richardson, 1846), an important fish cultivated in China. This study explores the interaction of water temperature and body weight on both energy utilization strategy and energy conversion efficiency to promote further healthy culture of yellow catfish. Fish with body weights of 6 g (Group S), 16 g (Group M) and 35 g (Group B) were reared in 15 circular glass steel cylinders 80 cm in diameter × 70 cm in height (180 L) at water temperatures of 21, 24, 27, 30 and 33°C (3 replicates for each temperature) for 42 days to investigate effects of water temperature and body weight on the feeding, growth, digestion and energy budget in yellow catfish. Results showed that the levels of dry matter, protein and energy in the body were significantly affected by water temperature (p < .05). Feeding, growth, feed conversion efficiency, digestion and energy allocation parameters were significantly related to both water temperature and body weight (p < .05). Yellow catfish had higher maximal food consumption (C_max), food intake rate, specific growth rate, food conversion efficiency, appear digestibility coefficient, and growth energy allocation (G) at 24–30°C, and optimal growth at a water temperature of 27°C. Two‐factor analysis of variance revealed that there was reciprocation of both water temperature and body weight on the above parameters. At the optimal temperature of 27°C, the value of energy for growth (G) was the highest, and the value of energy for feces (F) produced was the lowest. Yellow catfish with various body weights had energy budget equations of 100 A = 63.70 R + 36.30 G in Group S, 100 A = 62.54 R + 37.46 G in Group M, and 100 A = 67.47 R + 32.53 G in Group B if the equations were described as percentage of the proportion of the assimilation energy. Therefore, the optimal temperature was 27°C according to its feeding, growth and digestion.     

CDC25B is associated with the risk of hepatocellular carcinoma,but not related to persistent infection of hepatitis B virus in a Chinese population

The cell division cycle 25 (CDC25) gene members, including CDC25A, CDC25B and CDC25C, are reported to be associated with several human cancers. Here, we aim to investigate the association of functional polymorphisms of CDC25 gene family with the risk of hepatocellular carcinoma (HCC) and persistent infection of Hepatitis B virus (HBV) in a Chinese HBV-related population. First, we used bioinformatics tools to systematically screen functional polymorphisms within CDC25 gene family. Second, we evaluated the effects of candidate polymorphisms by recruiting 790 HCC cases, 709 persistent HBV carriers (PHC), and 741 subjects with HBV natural clearance (SHNC). MassARRAY platform was used for genotyping. At last, we conducted functional prediction and assay to further explore the pathogenic mechanism of the identified polymorphism. Our results demonstrated that CDC25B rs2295348 played a protective role in HCC risk in a HBV-related Chinese population (adjusted odds ratio [OR]?=?0.77, 95% confidence interval [CI] 0.65–0.93, P?=?0.006). It showed a more significantly reduced HCC risk in the SHNC population (adjusted OR?=?0.73, 95% CI 0.59–0.89, P?=?0.002). However, we did not observe the association between CDC25B rs2295348 and the risk of persistent HBV infection. Further functional prediction and assay demonstrated that the mutant A allele of CDC25B rs2295348 might significantly decrease gene expression to modify the HCC risk. Our results suggest that CDC25B rs2295348 may confer a protective effect on HCC risk in a HBV-related Chinese population, but do not influence the susceptibility to persistent HBV infection.

     

Retracted: In vivo and in vitro effects of microRNA-221 on hepatocellular carcinoma development and progression through the JAK–STAT3 signaling pathway by targeting SOCS3

Hepatocellular carcinoma (HCC), as the third leading cancer-caused deaths, prevails with high mortality, and affects more than half a million individuals per year worldwide. A former study revealed that microRNA-221 (miR-221) was involved in cell proliferation of liver cancer and HCC development. The current study aims to evaluate whether miR-221 targeting SOCS3 affects HCC through JAK–STAT3 signaling pathway. A series of miR-221 mimic, miR-221 inhibitor, siRNA against SOCS3, and SOCS3 plasmids were introduced to SMMC7721 cells with the highest miR-221 expression assessed. The expression of JAK–STAT3 signaling pathway–related genes and proteins was determined by Western blot analysis. Cell apoptosis, viability, migration, and invasion were evaluated by means of flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, and transwell assays, respectively. HCC xenograft in nude mice was performed to measure HCC tumor growth. miR-221 was found to be highly expressed but SOCS3 was poorly expressed in HCC tissues. miR-221 expression was correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) of HCC, and SOCS3 expression was correlated with LNM, differentiation and TNM of HCC. SOCS3 is a target gene of miR-221. MiR-221 mimic or si-SOCS3 exposure was found to induce cell viability, migration, and invasion, and reduce apoptosis. MiR-221 inhibitor was observed to have inhibitory effects on HCC cell proliferation, migration, and invasion. Moreover, the expression of JAK–STAT3 signaling pathway was suppressed by miR-221 inhibitor. Downregulated miR-221 expression could promote its target gene SOCS3 to inhibit the proliferation, invasion and migration of HCC cells by repressing JAK–STAT3 signaling pathway.     

Mathematical modeling of the indole-3-butyric acid applications on rooting of northern highbush blueberry (<Emphasis Type="Italic">Vaccinium corymbosum</Emphasis> L.) softwood-cuttings

The objective of the present study is to develop a mathematical model to predict the effect of indole-3-butyric acid (IBA) on mean rooting (%) and mean root growth of northern highbush blueberry cultivars (Vaccinium corymbosum L.). The best estimating equations for the rooting (%) and root growth are formulized as: RG = (5.672183) + [0.002851 × (IBA)] − [2.0E⁻⁶ × (IBA)2] + (−0.27211 × Cv.) and R = (82.00649) + [0.030801 × (IBA)] − [2,4E⁻⁵ × (IBA)2] − [2.36218 × (Cv.)] where RG is root growth, R is rooting, IBA is indole-3-butyric acid (ppm) and Cv. is cultivar. Cultivars are Ivanhoe [1], Jersey [2], Rekord [3], Northland [4], Berkeley [5] and Bluejay [6]. The numbers given in square brackets represent the blueberry cultivars for the equations. Multiple regression analysis was carried out until the least sum of squares (R2) was obtained. R ² value 0.90 for rooting and 0.95 for root growth. Standard errors were found to be significant at the p < 0.001 level. The actual rooting differed to the blueberry cultivars and it was between 57.76 and 83.23% while estimated rooting percentage calculated by the produced mathematical model was between 59.04 and 83.80%.     

Development and validation of robust metabolism-related gene signature in the prognostic prediction of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Given metabolic reprogramming in tumours was a crucial hallmark, several studies have demonstrated its value in the diagnostics and surveillance of malignant tumours. The present study aimed to identify a cluster of metabolism-related genes to construct a prediction model for the prognosis of HCC. Multiple cohorts of HCC cases (466 cases) from public datasets were included in the present analysis. (GEO cohort) After identifying a list of metabolism-related genes associated with prognosis, a risk score based on metabolism-related genes was formulated via the LASSO-Cox and LASSO-pcvl algorithms. According to the risk score, patients were stratified into low- and high-risk groups, and further analysis and validation were accordingly conducted. The results revealed that high-risk patients had a significantly worse 5-year overall survival (OS) than low-risk patients in the GEO cohort. (30.0% vs. 57.8%; hazard ratio [HR], 0.411; 95% confidence interval [95% CI], 0.302–0.651; p < 0.001) This observation was confirmed in the external TCGA-LIHC cohort. (34.5% vs. 54.4%; HR 0.452; 95% CI, 0.299–0.681; p < 0.001) To promote the predictive ability of the model, risk score, age, gender and tumour stage were integrated into a nomogram. According to the results of receiver operating characteristic curves and decision curves analysis, the nomogram score possessed a superior predictive ability than conventional factors, which indicate that the risk score combined with clinicopathological features was able to achieve a robust prediction for OS and improve the individualized clinical decision making of HCC patients. In conclusion, the metabolic genes related to OS were identified and developed a metabolism-based predictive model for HCC. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was approved.     

Prognostic value of tumour microenvironment-related genes by TCGA database in rectal cancer

Rectal cancer is a common malignant tumour and the progression is highly affected by the tumour microenvironment (TME). This study intended to assess the relationship between TME and prognosis, and explore prognostic genes of rectal cancer. The gene expression profile of rectal cancer was obtained from TCGA and immune/stromal scores were calculated by Estimation of Stromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) algorithm. The correlation between immune/stromal scores and survival time as well as clinical characteristics were evaluated. Differentially expressed genes (DEGs) were identified according to the stromal/immune scores, and the functional enrichment analyses were conducted to explore functions and pathways of DEGs. The survival analyses were conducted to clarify the DEGs with prognostic value, and the protein-protein interaction (PPI) network was performed to explore the interrelation of prognostic DEGs. Finally, we validated prognostic DEGs using data from the Gene Expression Omnibus (GEO) database by PrognoScan, and we verified these genes at the protein levels using the Human Protein Atlas (HPA) databases. We downloaded gene expression profiles of 83 rectal cancer patients from The Cancer Genome Atlas (TCGA) database. The Kaplan-Meier plot demonstrated that low-immune score was associated with worse clinical outcome (P = .034), metastasis (M1 vs. M0, P = .031) and lymphatic invasion (+ vs. -, P < .001). A total of 540 genes were screened as DEGs with 539 up-regulated genes and 1 down-regulated gene. In addition, 60 DEGs were identified associated with overall survival. Functional enrichment analyses and PPI networks showed that the DEGs are mainly participated in immune process, and cytokine-cytokine receptor interaction. Finally, 19 prognostic genes were verified by GSE17536 and GSE17537 from GEO, and five genes (ADAM23, ARHGAP20, ICOS, IRF4, MMRN1) were significantly different in tumour tissues compared with normal tissues at the protein level. In summary, our study demonstrated the associations between TME and prognosis as well as clinical characteristics of rectal cancer. Moreover, we explored and verified microenvironment-related genes, which may be the potential key prognostic genes of rectal cancer. Further clinical samples and functional studies are needed to validate this finding.