scholarly journals Average daily gain divergence in beef steers is associated with altered plasma metabolome and whole blood immune-related gene expression

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Ibukun M Ogunade ◽  
Megan McCoun

Abstract We evaluated the plasma amine/phenol- and carbonyl-metabolome and whole-blood immune gene expression profiles in beef steers with divergent average daily gain (ADG). Forty-eight Angus crossbred beef steers (21 days postweaning; 210 ± 8.5 kg of body weight) were fed the same total mixed ration ad libitum for 42 days with free access to water. After 42 days of feeding, the steers were divided into two groups of lowest (LF: n = 8) and highest ADG (HF: n = 8). Blood samples were taken from all steers. The blood samples from LF and HF steers were used for further analysis. A subsample of the whole blood was immediately transferred into RNA-protect tubes for RNA extraction and messenger RNA expressions of 84 genes involved in innate and adaptive immune responses. Another subsample of the whole blood was immediately centrifuged to harvest the plasma for subsequent metabolome analysis. The average daily dry matter intake of the steers in LF and HF was 6.08 kg ± 0.57 and 6.04 kg ± 0.42, respectively, and was similar between the two groups (P = 0.72). The ADG (1.09 kg ± 0.13) of LF was lower (P = 0.01) than that of HF (1.63 kg ± 0.20). The expressions of 10 immune-related genes were upregulated (FC ≥ 1.2; P ≤ 0.05) in HF steers; these genes were involved in viral pathogen recognition and eradication, defense against intracellular and extracellular pathogens and parasites, and immune response homeostasis. A total number of 42 carbonyl-containing metabolites and 229 amine/phenol-containing metabolites were identified in the plasma samples of both groups. No alteration in carbonyl-metabolome was detected. Ten metabolites with immunomodulatory, anti-inflammatory, and reactive oxygen-scavenging properties were greater (FDR ≤ 0.05) in HF steers, whereas eight metabolites including arginine, phenylalanine, guanidoacetic acid, and aspartyl-threonine were greater in LF steers. This study demonstrated that beef steers with divergent ADG had altered plasma amine/phenol metabolome and immune-related gene expressions in the blood. Notably, plasma metabolites and immune-related genes of great health benefits were greater in steers with high ADG.

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 399-400
Author(s):  
Ibukun M Ogunade

Abstract We evaluated the whole-blood immune-related gene expression profiles in beef steers divergent in average daily gain (ADG). Forty-eight healthy Angus crossbred beef steers (21 d post-weaning; 210 ± 12 kg of BW) from a single source were housed in individual slatted floor pens and were fed similar corn silage-based total mixed ration ad libitum. After 42 days of feeding, the steers were assigned into two groups with lowest ADG (LF: n = 8) and highest (HF: n = 8) ADG. The average daily DM intake of the steers in LF and HF were 6.08 kg ± 0.57 and 6.04 kg ± 0.42, respectively, and was similar between the two groups (P = 0.72). Whole blood samples were taken from both LF and HF steers and were immediately processed for RNA extraction. Messenger RNA expressions of 84 genes related to innate and adaptive immune responses were analyzed using the RT2 Profiler cow innate and adaptive immune responses PCR Array (PABT-052ZA; Qiagen). Immune genes with FC ≥ 1.2 or ≤ 0.83 having P-value ≤ 0.05 were considered to be differentially expressed. A total number of 11 immune genes were differentially expressed between HF and LF steers. The mRNA expressions of 10 immune genes (IRF3, TLR3, CCR4, MAPK3, TYK2, STAT3, STAT4, STAT6, CCR8, and GATA3) were upregulated in HF steers; these genes were involved in viral pathogen recognition and eradication, defense against intracellular and extracellular pathogens and parasites, and immune response homeostasis. A pro-inflammatory cytokine, IL-2, was upregulated in LF steers. These findings demonstrate that beef steers with divergent ADG had differential expressions of immune-related genes in the blood and future studies are needed to evaluate the mechanisms that cause differences in the expression of these immune genes and how these mechanisms can be employed to drive improved animal performance.


Author(s):  
Xianghong Zhou ◽  
Shi Qiu ◽  
Di Jin ◽  
Kun Jin ◽  
Xiaonan Zheng ◽  
...  

Abstract Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p<0.001). Combined with multiple clinical pathological factors, the results of multivariate analyses confirmed that this signature was an independent predictor of OS (HR, 3.548; 95%CI, 2.096−6.006; p<0.001). The results of immune infiltration analysis demonstrated that the abundance of multiple tumor-infiltration lymphocytes such as CD8+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 189-190
Author(s):  
Godstime A Taiwo ◽  
Ibukun M Ogunade

Abstract We examined the effects of dietary supplementation of a blend of mannan and glucan on the growth performance, diet digestibility, and whole-blood immune gene expression of newly weaned beef steers during a 42-d receiving period. Forty-eight newly weaned Angus crossbred steers (2 d post-weaning; 199 ± 13 kg of initial BW) were randomly assigned to 1 of 2 treatments: basal diet with no additive (CON; n = 24) or a basal diet top-dressed with 5 g of a blend of mannan and glucan (MANGLU; n = 24). Average daily gain (ADG) was calculated from weekly BW. Blood samples were collected on days 0, 14, and 42 for measurement of plasma glucose and NEFA. Expression of 84 immune-related genes was analyzed on blood samples collected on day 42. Beginning on days 37 to 42, total mixed ration, refusals, and fecal samples were collected once daily to determine apparent total tract digestibility of DM, CP, NDF, and ADF using indigestible NDF as an internal marker. Immune gene expression data was analyzed using a GeneGlobe Data Analysis Center. All other data were analyzed as a randomized complete block design using the GLIMMIX procedure of SAS. Over the 42-d feeding trial, MANGLU tended to increase final BW (P = 0.07) and ADG (P = 0.06). Compared to CON, beef steers fed supplemental MANGLU had greater DM digestibility (P = 0.03) and tended to have greater NDF digestibility (P = 0.09). No treatment effects (P &gt; 0.10) on plasma glucose and NEFA on d 14 and 42 were detected. Compared with CON, MANGLU increased (P ≤ 0.05) the expression of five immune-related genes involved in recognition of and mounting immune defense against microbial pathogens. In conclusion, this study demonstrated that supplemental MANGLU enhances beef cattle immunocompetence and productivity during feedlot receiving period.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 423-423
Author(s):  
Naoki Takahashi ◽  
Yutaka Matano ◽  
Akihiko Tsujibata ◽  
Kozue Murayama ◽  
Shoichi Miyazawa ◽  
...  

423 Background: Immune checkpoints inhibitor (ICI) is effective and approved in some solid tumors including advanced gastric cancer (GC). Peritoneal dissemination is known as a poor prognostic factor and was reported to be associated with the resistance to ICI according to the previous reports. The aim of our study is to compare the immune-related gene expression between primary site and peritoneal lesion in advanced GC patients. Methods: Among advanced GC patients, we selected those who underwent surgical resection for both primary and peritoneal lesions simultaneously. Formalin-fixed paraffin-embedded (FFPE) tumor tissues of primary and peritoneal lesions were prepared and RNA was extracted by Maxwell RSC RNA FFPE kit (Promega). Immune-related gene expression was evaluated by using nCounter Max Analysis System (NanoString). We used nCounter PanCancer Immune Profiling Panel Kit which includes 770 immune-related genes. Results: Immune-related gene expression was evaluated by using twenty-four FFPE tumor tissues in twelve GC patients. Scatter plot and hierarchical clustering analyses showed that the pattern of immune-related gene expression was not much different between primary and peritoneal lesions beyond the individual differences. Regarding the T cell function, high expression of Immune-related genes was widely detected in patients with EB virus-positive (n = 2) and HER2-positive (n = 1). Gene expressions such as CD70, FAS, MAF and IL-3 were higher in peritoneal lesion compared with primary lesion (p < 0.05). Whereas, expressions of F2RL1 and IL-11 were lower in peritoneal lesion compared with primary lesion (p < 0.05). Conclusions: Our study indicated that there was not much difference of Immune-related gene expression between primary and peritoneal lesion in advanced GC patients. Positive status of EB virus and HER2 may be associated with high expression of immune-related genes. Further analysis to evaluate immune-related gene expression between primary and metastatic site may contribute the further understanding of cancer immunity in advanced GC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Zhang ◽  
Ping Chen ◽  
Qiang Zhou ◽  
Hongyan Wang ◽  
Qingquan Hua ◽  
...  

The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, very limited robust and reliable immunological biomarkers have been developed that are capable of estimating prognosis in HNSCC patients. In this study, we aimed to identify the effects of novel immune-related gene signatures (IRGs) that can predict HNSCC prognosis. Based on gene expression profiles and clinical data of HNSCC patient cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, a total of 439 highly variable expressed immune-related genes (including 239 upregulated and 200 downregulated genes) were identified by using differential gene expression analysis. Pathway enrichment analysis indicated that these immune-related differentially expressed genes were enriched in inflammatory functions. After process screening in the training TCGA cohort, six immune-related genes (PLAU, STC2, TNFRSF4, PDGFA, DKK1, and CHGB) were significantly associated with overall survival (OS) based on the LASSO Cox regression model. Integrating these genes with clinicopathological features, a multivariable model was built and suggested better performance in determining patients’ OS in the testing cohort, and the independent validation cohort. In conclusion, a well-established model encompassing both immune-related gene signatures and clinicopathological factors would serve as a promising tool for the prognostic prediction of HNSCC.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 420-421
Author(s):  
Ibukun M Ogunade ◽  
Devan M Compart ◽  
Andres A Pech-Cervantes

Abstract We examined the effects of dietary supplementation of a Saccharomyces cerevisiae-based direct-fed microbial on the performance, whole-blood immune gene expression, and plasma metabolome of beef steers during a 42-d receiving period. Forty newly weaned Angus crossbred steers (7 d post-weaning; 210 ± 12 kg of BW) were stratified by BW and randomly assigned to 1 of 2 treatments: basal diet with no additive (CON; n = 20) or a basal diet top-dressed with 19 g of the DFM (PROB; n = 20). PROB (PMI, Arden Hills, MN) is an optimized blend of 6.2 × 1011 cfu/g of S. cerevisiae, 3.5 × 1010 cfu/g of a mixture of Enterococcus lactis, Bacillus subtilis, Enterococcus faecium, and L. casei. Daily DMI and weekly body weights were measured to calculate average daily gain (ADG) and feed efficiency (FE). Expression of 84 immune-related genes was analyzed on whole blood samples collected on days 21 and 42. Plasma metabolome was analyzed on day 42. The data were analyzed using the GLIMMIX procedure of SAS with treatment as a fixed effect and BW as a random effect. Compared with CON, PROB increased or tended to increase final body weight (P = 0.01), ADG (P = 0.04), and FE (P = 0.10). Compared with CON, PROB increased (P ≤ 0.05) the expression of seven immune-related genes involved in detecting pathogen-associated molecular patterns and T-cell differentiation. Plasma metabolome analysis revealed an increase (P ≤ 0.05) in concentrations of ten metabolites involved in protecting the animals against inflammation in steers fed PROB diet. This study demonstrated that supplementation of PROB improved the performance and health of newly weaned beef steers during a 42-d receiving period.


2021 ◽  
Author(s):  
Ying Zhong ◽  
Zhe Wang ◽  
Yidong Zhou ◽  
Feng Mao ◽  
Yan Lin ◽  
...  

Abstract Background: Immunotherapy plays an increasingly important role in the treatment of advanced female breast cancer, which has the highest mortality rate among malignant tumors. The purpose of this study was to identify immune-related genes associated with breast cancer prognosis as possible targets of immunotherapy, and their related biological processes and signaling pathways.Methods: Clinical data and gene expression profiles of patients with breast cancer were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and divided into training (n = 1053) and verification (n = 508) groups. CIBERSORT was used to predict differences in immune cell infiltration in patient subsets stratified according to risk. Gene Ontology (GO) enrichment analysis was used to identify pathways associated with immune-related genes in patient subsets stratified according to risk.Results: The prognostic model composed of 27 immune-related gene pairs significantly distinguished between high- and low-risk patients. Univariate and multivariate analyses indicated that the model was an independent prognostic factor for breast cancer. Among the identified genes, APOBEC3G, PLXNB1, and C3AR1 had not been previously studied in breast cancer and warrant further exploration. CCR chemokine receptor binding, regulation of leukocyte-mediated cytotoxicity, T cell migration, T cell receptor complex, and other pathways were significantly enriched in low-risk patients. M2 and M0 macrophages were more highly expressed in high-risk than in low-risk patients. CD8+ T cells and naïve B cells were more abundant in low-risk than in high-risk patients.Conclusion: The immune-related gene pairs prognostic model developed in the current study can help assess breast cancer prognosis and provides a potential target and research direction for breast cancer immunotherapy in the future.


Author(s):  
Ibukun M Ogunade ◽  
Godstime Taiwo ◽  
Zaira M Estrada-Reyes ◽  
Y Jiang ◽  
Andres A Pech-Cervantes ◽  
...  

Abstract We examined the effects of dietary supplementation of a blend of mannan and glucan on the growth performance, energy status, and whole-blood immune gene expression of newly weaned beef steers during a 42 d receiving period. Forty eight newly weaned Angus crossbred steers (2 d post-weaning; 199 ± 13 kg of initial BW) from a single source were stratified by BW and randomly assigned to 1 of 2 treatments: basal diet with no additive (CON; n = 24) or a basal diet top-dressed with 5 g of a blend of mannan and glucan (MANGLU; n = 24). Average daily gain (ADG) and feed efficiency (FE) from days 1 – 14, 15 – 42, and 1 – 42 were calculated from daily dry matter intake (DMI) and weekly BW. Blood samples were collected on days 0, 14, and 42 for measurement of plasma glucose and NEFA. Blood samples collected on days 14 and 42 were composited for each steer for untargeted carbonyl-metabolome analysis (measurement of carbonyl-containing metabolites). Expression of 84 immune-related genes was analyzed on blood samples collected on day 42. Beginning on days 37 to 42, total mixed ration, refusals, and fecal samples were collected once daily to determine apparent total tract digestibility of DM, CP, NDF, and ADF using indigestible NDF as an internal marker. Over the 42-d feeding trial, supplemental MANGLU tended to increase final BW (P = 0.07) and ADG (P = 0.06). Compared to CON, beef steers fed supplemental MANGLU had greater (P = 0.01) DMI during the first 14 d, greater DM digestibility (P = 0.03), and tended to have greater NDF digestibility (P = 0.09). No treatment effects (P &gt; 0.10) on plasma glucose and NEFA on d 14 and 42 were detected; however, carbonyl-metabolome analysis revealed increased (FDR ≤ 0.05) plasma concentrations of galactose and glyceraldehydes, and altered (FDR ≤ 0.05) concentrations of some microbiome-derived metabolites in beef steers fed MANGLU. Compared with CON, MANGLU increased (P ≤ 0.05) the expression of five immune-related genes involved in recognition of and mounting immune defense against microbial pathogens. In conclusion, the results of this study demonstrated that supplemental MANGLU enhances beef cattle immunocompetence and productivity during feedlot receiving period.


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