Expression Profiles Of Immune-related Genes Research Articles

Effect of dietary fucoidan on innate immune response of Procambarus clarkii and disease resistance against white spot syndrome virus

This study has been investigated the effect of dietary fucoidan on the innate immune response of crayfish (Procambarus clarkii) and the disease resistance against white spot syndrome virus (WSSV) infection. Adding fucoidan (30 mg/kg) to the diet can dramatically improved the survival rate of crayfish after WSSV infection and also can reduce the copy number of WSSV. The result of qRT-PCR demonstrated that fucoidan treatment can increase the expression profile of immune-related genes, such as NF-κB and prophenoloxidase. Further evidence indicates that fucoidan also had the influence on three immune parameters, which consist of the total number of hemocyte (THC), phenoloxidase activity (PO) and superoxide dismutase activity (SOD) in crayfish. The hemocytes apoptosis of crayfish post WSSV-infected and uninfected crayfish were both increased significantly after treating with 30 mg/kg fucoidan. Dietary fucoidan delayed and reduced the mortality after oral WSSV challenge, and decreased WSSV copies in 96 h after challenge. Our research demonstrated that fucoidan can be used to the regulation of innate immunity and induce immune protection effect of crayfish from WSSV infection, whether for treatment or prevention.

Identification of an Immune-Related Gene Signature to Improve Prognosis Prediction in Colorectal Cancer Patients.

BackgroundDespite recent advance in immune therapy, great heterogeneity exists in the outcomes of colorectal cancer (CRC) patients. In this study, we aimed to analyze the immune-related gene (IRG) expression profiles from three independent public databases and develop an effective signature to forecast patient’s prognosis.MethodsIRGs were collected from the ImmPort database. The CRC dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another two CRC datasets from the Gene Expression Omnibus (GEO). Gene function enrichment analysis was conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.ResultsThe three datasets had 487, 579, and 224 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B, and IL20RB) was developed through feature selection that showed good differentiation between the low- and high-risk groups in the training set (p < 0.001), which was later confirmed in the two validation groups (log-rank p < 0.05). The signature outperformed tumor TNM staging for survival prediction. GO and KEGG functional annotation analysis suggested that the signature was significantly enriched in metabolic processes and regulation of immunity (p < 0.05). When combined with clinical risk factors, the model showed robust prediction capability.ConclusionThe immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could provide insight for personalized cancer management.

PSII-1 Beef steers divergent in average daily gain have differential expressions of immunity-related genes in whole blood

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.

Development of an Immunogenomic Landscape-Based Prognostic Index of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the eighth leading cancer by incidence worldwide, with approximately 700,000 new cases in 2018 (accounting for 11% of all cancers). The occurrence and development of tumors are closely related to the immunological function of the body and sensitivity to treatment schemes as well as prognosis. It is urgent for clinicians to systematically study patients’ immune gene maps to help select a treatment plan and analyze the potential to cure HNSCC. Here, the transcriptomic data of HNSCC samples were downloaded from The Cancer Genome Atlas (TCGA), and 4,793 genes differentially expressed in normal and cancer tissues of HNSCC were identified, including 1,182 downregulated and 3,611 upregulated genes. From these genes, 400 differentially expressed immune-related genes (IRGs) were extracted, including 95 downregulated genes and 305 upregulated genes. The prognostic values of IRGs were evaluated by univariate Cox analysis, and 236 genes that were significantly related to the overall survival (OS) of patients were identified. The signaling pathways that play roles in the prognosis of IRGs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the expression profiles of IRGs and OS in 499 HNSCC patients based on TCGA dataset were integrated. Potential molecular mechanisms and characteristics of these HNSCC-specific IRGs were further explored with the help of a new prognostic index based on IRGs developed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A total of 64 hub genes (IRGs associated with prognosis) were markedly associated with the clinical outcome of HNSCC patients. KEGG functional enrichment analysis revealed that these genes were actively involved in several pathways, e.g., cytokine–cytokine receptor interaction, T-cell receptor signaling, and natural killer cell-mediated cytotoxicity. IRG-based prognostic signatures performed moderately in prognostic predictions. Interestingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. These data screened several IRGs of clinical significance and revealed drivers of the immune repertoire, demonstrating the importance of a personalized IRG-based immune signature in the recognition, surveillance, and prognosis of HNSCC.

Immunologic Predictors for Clinical Responses in Patients with Myelodysplastic Syndromes Treated with Immune Checkpoint Blockade

Immunologic Predictors for Clinical Responses in Patients with Myelodysplastic Syndromes Treated with Immune Checkpoint Blockade

Immune prognostic risk score model in acute myeloid leukemia with normal karyotype.

Acute myeloid leukemia with normal karyotype (NK-AML) is a group of diseases with high heterogeneity and immunological processes are significantly associated with its initiation and development. The implication of the immunogenomic landscape in the prognosis of patients with NK-AML has remained largely elusive. In the present study, the expression profiles of immune-related genes (IRGs) were examined and their association with overall survival (OS) was determined in 60 patients with NK-AML from The Cancer Genome Atlas dataset and 104 patients from the Gene Expression Omnibus (GEO) dataset no. GSE71014. Univariate Cox regression analysis was used to identify 42 and 203 IRGs in the two respective cohorts, which were significantly associated with OS in NK-AML. A risk model was constructed based on the regression coefficient and expression values of nine survival-associated IRGs shared between the two datasets [zinc finger CCCH-type containing, antiviral 1 like; transferrin receptor; suppressor of cytokine signaling 1; ELAV like RNA binding protein 1; roundabout guidance receptor 3; unc-93 homolog B1, Toll-like receptor signaling regulator; protein tyrosine phosphatase non-receptor type 6; interleukin 2 receptor subunit alpha (IL2RA) and IL3RA]. Using this risk model, patients with NK-AML may be divided into high- and low-risk groups in prognostic predictions. The area under the receiver operating characteristic curve for predicting OS was 0.793. The prognostic role of this risk model was successfully verified in another independent cohort (GEO dataset no. GSE71014). The prognostic risk score was positively associated with age and fms related receptor tyrosine kinase 3 mutation and correlated with infiltration by T regulatory cells. In conclusion, the results of the present study provided an IRG score model for prognostic stratification of adult patients with NK-AML, as well as further insight into the implication of IRGs in NK-AML that may lead to the development of novel immunotherapy approaches for this disease.

Machine learning reveals a PD-L1-independent prediction of response to immunotherapy of non-small cell lung cancer by gene expression context.

Current predictive biomarkers for PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-directed immunotherapy in non-small cell lung cancer (NSCLC) mostly focus on features of tumour cells. However, the tumour microenvironment and immune context are expected to play major roles in governing therapy response. Against this background, we set out to apply context-sensitive feature selection and machine learning approaches on expression profiles of immune-related genes in diagnostic biopsies of patients with stage IV NSCLC. RNA expression levels were determined using the NanoString nCounter platform in formalin-fixed paraffin-embedded tumour biopsies obtained during the diagnostic workup of stage IV NSCLC from two thoracic oncology centres. A 770-gene panel covering immune-related genes and control genes was used. We applied supervised machine learning methods for feature selection and generation of predictive models. Feature selection and model creation were based on a training cohort of 55 patients with recurrent NSCLC treated with PD-1/PD-L1 antibody therapy. Resulting models identified patients with superior outcomes to immunotherapy, as validated in two subsequently recruited, separate patient cohorts (n=67, hazard ratio=0.46, p=0.035). The predictive information obtained from these models was orthogonal to PD-L1 expression as per immunohistochemistry: Selecting by PD-L1 positivity at immunohistochemistry plus model prediction identified patients with highly favourable outcomes. Independence of PD-L1 positivity and model predictions were confirmed in multivariate analysis. Visualisation of the models revealed the predictive superiority of the entire 7-gene context over any single gene. Using context-sensitive assays and bioinformatics capturing the tumour immune context allows precise prediction of response to PD-1/PD-L1-directed immunotherapy in NSCLC.

Comparative analysis of key immune protection factors in H9N2 avian influenza viruses infected and immunized specific pathogen–free chicken

H9N2 avian influenza viruses (AIV) continue to circulate in vaccinated chicken flocks in China, which prompted us to investigate the differential immune protection factors induced by H9N2 AIV infection and immunization for analyzing the reason of protection deficiency of H9N2 AIV inactivated vaccine. In this study, we firstly explored virus-induced optimal immune responses in chicken after H9N2 AIV infection. And, we found that H9N2 hemagglutination inhibition (HI) antibody level, antiviral interferon-stimulated genes including 2′,5’-oligoadenylate synthetase-like and myxovirus resistance 1, CD8+ T cell response in peripheral blood lymphocytes (PBL) accompanied by the cytotoxicity-associated genes, including poly (ADP-ribose) polymerase and IFN-r play important roles in defending against H9N2 infection. Besides, we observed that vaccine immunization triggered the similar H9N2 HI antibody level as viral infection, the increase of CD4+ T cell percentage instead of CD8+ T cell percentage in PBL. Moreover, we further made a comparative analysis of immune-related gene expression profile in PBL and lung after H9N2 AIV infection and immunization, respectively. The results showed that vaccine immunization contributed to the up-regulation of Th2 cytokine. But the deficiency of cytotoxicity-associated genes induced by H9N2 AIV inactivated vaccine may be the potential key reason of protection deficiency. These findings provide evidence and direction for developing effective H9N2 AIV vaccines.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile

Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction. Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype. Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.

Effects of propolis on the immune enhancement of the formalin‐inactivated Aeromonas salmonicida vaccine

Furunculosis caused by Aeromonas salmonicida is a major threat to salmonids throughout all their life stages. Vaccination against A. salmonicida has been shown to provide effective protection in aquaculture. The success of many vaccines relies on their association with the appropriate adjuvant to increase their immunogenicity and ensure long-term protection. In this study, the effects of vaccines using propolis as adjuvants against furunculosis in rainbow trout (Oncorhynchus mykiss) were evaluated. The parameters evaluated included the relative percent survival (RPS), the specific IgM antibody level and the expression profiles of several immune-related genes in four tissues following immunization and challenge. The results showed that the experimental vaccines containing propolis as adjuvants (ExpVacPro group) could effectively protect the experimental fish against A. salmonicida infection with an RPS of 89.47%. The gene expression data revealed that ExpVacPro could induce the differential expression of the pro-inflammatory cytokines, MHC class Ⅰ, T-cell markers and Ig markers in immunized fish, with higher levels in liver and spleen than in head kidney and gill. ExpVacPro initially increased the expression of MHC I and IL8 genes in related pathways, and then gradually increased the expression of IL-1β and IgT genes for about 2 weeks. During the post-vaccination challenge, the expression levels of all detected genes were up-regulated especially for CD8 and IgT genes. The specific IgM antibody titres were significantly induced following immunization and challenge. In conclusion, the results indicated that propolis could improve potency and efficacy of formalin-inactivated A. salmonicida vaccine as adjuvants.

Abstract 1705: Identification of an immune gene expression signature for progression of breast ductal carcinoma in situ (dcis)

Abstract Introduction. DCIS is a potential precursor of invasive breast cancer (IBC). Immune escape might play a critical role in the transition from DCIS to IBC. We aim to identify an immune-related gene expression signature of DCIS to distinguish hazardous lesions, and to avoid the burden of overtreatment in women with less harmful DCIS. Since tumor-infiltrating lymphocytes (TILs) occur more frequently in hormone receptor-negative, Her-2 positive DCIS, we focused the analysis on this subtype. Methods. We performed a prospective nested case-control study involving women with pure DCIS (hormone receptor-negative, Her-2 positive, TILs ≥ 20%), treated with breast conservative surgery with or without radiotherapy. Cases were defined as women with DCIS developing subsequent ipsilateral breast event (IBE), controls as women with DCIS without IBE at 8 years of follow-up. Next-generation sequencing gene expression assay (Oncomine™ Immune Response Research Assay) targeting 395 genes associated with tumor-immune systems interactions was performed on RNA extracted from DCIS samples of 25 cases and 25 age- and radiotherapy-matched controls. In order to obtain reliable results, we considered adequate samples with mapped reads &amp;gt; 1 million and valid reads &amp;gt; 800.000. Normalized gene-level count data generated from the run were further processed with Affymetrix™. A Volcano plot was also employed in order to distinguish genes differently expressed between cases and controls according to the log-gene-level fold change and the ANOVA test (p values &amp;lt; 0.05). Univariate (Log-rank) and multivariate Cox proportional hazard models identified genes associated with the disease free survival. Results. Thirty-one samples (15 cases; 16 controls) reached the quality parameters. The analysis identified 11 genes with a significant different expression between cases and controls. The upregulation of three immune-related genes (VTCN1, NT5E and CMKLR1) remained significantly associated with disease free survival. Notably, VTCN1 and NT5E expressions were significantly associated with the risk of invasive local recurrence. Conclusions. This exploratory analysis of hormone receptor-negative, Her-2 positive DCIS with TILs ≥ 20% showed significant differences in immune-related gene expression profiles between women with subsequent IBE and controls. VTCN1 and NT5E may play an important role in immune surveillance mechanisms of DCIS and may be targeted by immune-based therapy to slow or prevent DCIS progression. These results are well worth further validation on future studies. Citation Format: Matteo Lazzeroni, Caternia Fumagalli, Federica Corso, Alberto Ranghiero, Debora Macis, Elena Guerini Rocco, Valentina Aristarco, Harriet Johansson, Aliana Guerrieri-Gonzaga, Davide Serrano, Andrea DeCensi, Sara Gandini, Massimo Barberis, Bernardo Bonanni. Identification of an immune gene expression signature for progression of breast ductal carcinoma in situ (dcis) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1705.

Antioxidant capacity, non-specific immunity, histopathological analysis and immune-related genes expression in Nile tilapia Oreochromis niloticus infected with Aeromonas schubertii

Aeromonas schubertii is a conditional pathogen widely distributed in aquatic environments, yet it was only recently reported as a causative pathogen in fish. This study investigated antioxidant capacity, non-specific immunity, histopathology and immune-related gene expression profiles in Nile tilapia Oreochromis niloticus injected with A. schubertii. The results show that A. schubertii infection stimulated the activation of antioxidant activity and non-specific immunity in Nile tilapia. Histopathological analysis revealed that inflammation existed in the liver, spleen, head kidney, brain and intestine of the infected fish. Quantitative real-time PCR was performed to measure mRNA expression levels of six immune-related genes (interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, transforming growth factor beta, interleukin-10 and heat shock protein 70) in the intestine and head kidney at different timepoints after experimental infection. The results demonstrated clear transcriptional activation of these immune-related genes in the intestine and head-kidney tissues. To our knowledge, this is the first study to investigate the host response to A. schubertii infection in a fish. These results will contribute to further understanding of the pathogenesis and host defense system in fishes following infection with A. schubertii.

Expression profiles of immune-related genes in coelomocytes during regeneration after evisceration in Apostichopus japonicus

A representative echinoderm, the sea cucumber Apostichopus japonicus has a special regeneration mechanism. The sea cucumber has no specific immune tissues or organs. Coelomocytes of sea cucumbers are involved in their cellular and humoral immunity. In this study, expression profiles of the main immune-related factors in sea cucumber coelomocytes were detected during coelomocyte regeneration after evisceration in A. japonicus. Immune-related factors Cu/Zn superoxide dismutase (Cu/Zn SOD), Catalase (CAT), C-type lysozyme (C-LYZ), Cathepsin D (CTSD), Melanotransferrin (MTF), Toll-like receptor (TLR), C-type lectin (C-LCT), Complement 3 (C3), Myeloid differentiation factor 88 (MYD88), Nuclear factor kappa-B (NF-κB), NF-κB inhibitor (IKB), TNF receptor-associated factor 6 (TRAF6), Peroxiredoxins (PRX), Nitric oxide synthase(NOS), Caspase-2 (CASP-2), Phenoloxidase (PO), and Glutathione Peroxidase(GPX), Heat shock protein 70 (HSP70) were detected by real-time fluorescent quantitative PCR at different time points during regeneration. The main immune-related genes in sea cucumber coelomocytes were significantly differentially expressed after evisceration, and an upregulation was observed for the majority of the considered genes. In summary, the discharge of viscera had a significant effect on expression of immune-related genes of sea cucumber coelomocytes. The expression level of each gene had a certain correlation with the sea cucumber regeneration process. The results provide reference data for the immune response of coelomocytes during regeneration.

Panel-derived TMB and immune-related GEP are associated with the response to immune checkpoint inhibitors (ICIs) in urothelial cancers.

e17047 Background: Tumor mutational burden (TMB) and gene expression profile (GEP) have emerged as potential biomarkers for the prediction of response to the immune checkpoint inhibitor (ICI) treatment. An interferon-g gene signature was shown recently to predict ICI response in a pan-cancer setting. For TMB, not only did TMB-high patients experience better clinical outcome with ICI, but panel-derived TMB was also shown to be comparable to the gold standard, TMB derived from whole exome sequencing. Here, we evaluate possible correlations between panel-derived TMB, as well as immune-related GEP, with ICI response in urothelial cancers. Methods: FFPE tumor tissues from 30 patients with urothelial cancers who had previously received ICI as monotherapies or combination with chemotherapies at Kaohsiung Chang Gung Memorial Hospital were retrospectively tested for targeted next-generation sequencing (ACTOnco) and quantitative PCR-based GEP (ACTTME), for the identification of nonsynonymous variants across 440 cancer-associated genes and expression levels of &gt; 90 immune-related genes, respectively. TMB was calculated by using the sequenced regions of ACTOnco to estimate the number of somatic nonsynonymous mutations per megabase of all protein-coding genes. For ACTTME, Cq values were normalized to internal control before group analysis. RECIST criteria were used to categorize tumor response to the treatment. Results: Patients were defined as responders (CR/PR) and non-responders (SD/PD) according to the RECIST criteria. In the ICI monotherapy cohort, the responders (n = 8) had significantly higher TMB than non-responders (n = 15) (Median 16.2 muts/Mb vs. 6.5 muts/Mb, p= 0.0035). In contrast, for the cohort receiving ICI combination therapy, several genes implicated in hypoxia (HIF1A), suppressive cell types (Treg &amp; MDSC) and immune checkpoint (PD-L2) were significantly elevated ( p&lt; 0.05) in the non-responder group by 2 to 8 folds. Conclusions: Despite the fact that the cohort size is small, this study showed panel-derived TMB, as well as immune-related GEP, can potentially serve as predictive biomarkers to identify urothelial cancer patients for immune checkpoint inhibitor therapy.

Immune-Related Prognostic Model in Colon Cancer: A Gene Expression-Based Study.

Mounting evidence supports that the malignant phenotypes of cancers are defined not only by the intrinsic activity of tumor cells but also by immune cells that are recruited and activated in tumor-related microenvironment. Here, we developed a diagnostic and prognostic model for colon cancer, based on expression profiles of immune-related genes and immune cell component. As a result, we found that B cell infiltration ratio, CD4+ T cells, as well as immune-related genes of TRIB3, CHGA, CASP7, LGALS4, LEP, NOX4, IL17A, and HSPD1 may be highly relevant with clinical outcome of colon cancer.

Prognostic role of PD-L1 and immune-related gene expression profiles in giant cell tumors of bone.

Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastatic tumor, with a relatively unpredictable clinical course. A retrospective series of 46 GCTB and a control group of 24 aneurysmal bone cysts (ABC) were selected with the aim of investigating the PD-L1 expression levels and immune-related gene expression profile, in correlation with clinicopathological features. PD-L1 and Ki67 were immunohistochemically tested in each case. Furthermore, comprehensive molecular analyses were carried out using NanoString technology and nCounter PanCancer Immune Profiling Panel, and the gene expression results were correlated with clinicopathological characteristics. PD-L1 expression was observed in 13/46 (28.3%) GCTB (and in 1/24, 4.2%, control ABC, only) and associated with a shorter disease free interval according to univariate analysis. Moreover, in PD-L1-positive lesions, three genes (CD27, CD6 and IL10) were significantly upregulated (p < 0.01), while two were downregulated (LCK and TLR8, showing borderline significance, p = 0.06). Interestingly, these genes can be related to maturation and immune tolerance of bone tissue microenvironment, suggesting a more immature/anergic phenotype of giant cell tumors. Our findings suggest that PD-L1 immunoreactivity may help to select GCTB patients with a higher risk of recurrence who could potentially benefit from immune checkpoint blockade.

Acute BPA exposure-induced oxidative stress, depressed immune genes expression and damage of hepatopancreas in red swamp crayfish Procambarus clarkii

Bisphenol A is a typical endocrine disrupting chemicals (EDCs) and produce various toxic effects on animals due to its potential endocrine disruption, oxidative damage effect, mutagenic effect and hypomethylation. To study its effect on the immune system of crustaceans, the Procambarus clarkii were utilized to detect the immune related indicators after 225 μg/L BPA exposure for 1 week. Hepatopancreatic histology and ultrastructure analysis showed that the brush border disappeared, the lumen increased, and the connection between the hepatic tubules fade away in BPA treated group. BPA could significantly increase the level of ROS, inhibit the activities of antioxidant-related enzymes (SOD, POD, and CAT), and thereby cause the oxidative stress. The enzyme activities of AKP, ACP and lysozyme in hepatopancreas after BPA exposure were also depressed even after Aeromonas hydrophila infections. The relative expression profiles of immune-related genes after BPA exposure and bacterial infection showed suppressed trends of most selected genes. Under A. hydrophila infections, the cumulative mortality of 225 μg/L BPA-treated crayfish was significantly higher than other groups. All these results indicated that BPA exposure had adverse effects on the immune ability of P. clarkii. The present study will provide an important foundation for further understanding the effects of EDCs on crustacean immune functions.

Development of an immune-related prognostic index associated with hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC), an inflammation-associated cancer induced by a variety of etiological factors, is still one of the most prevalent and lethal cancers in human population. In this study, the expression profiles of immune-related genes (IRGs) were integrated with the overall survival (OS) of 378 LIHC patients based on the Cancer Genome Atlas (TCGA) dataset. Moreover, the differentially expressed and survival related IRGs among LIHC patients were predicted through the computational difference algorithm and COX regression analysis. As a result, 7 genes, including HSPA4, S100A10, FABP6, CACYBP, HDAC1, FCGR2B and SHC1, were retrieved to construct a predictive model associated with the overall survival (OS) of LIHC patients. Typically, the as-constructed model performed moderately in predicting prognosis, which was also correlated with tumor grade. Functional enrichment analysis revealed that the genes of high-risk group were actively involved in mRNA binding and the spliceosome pathway. Intriguingly, the prognostic index established based on IRGs reflected infiltration by multiple types of immunocytes. Our findings screen several IRGs with clinical significance, reveal the drivers of immune repertoire, and illustrate the importance of a personalized, IRG-based immune signature in LIHC recognition, surveillance, and prognosis prediction.

Molecular classification of breast cancer using the mRNA expression profiles of immune-related genes

Breast cancer is the most lethal cancer in women and displaying a broad range of heterogeneity in terms of clinical, molecular behavior and response to therapy. Increasing evidence demonstrated that immune-related genes were an important source of prognostic information for several types of tumors. In this study, the k-mean clustering was applied to gene expression data from the immune-related genes, two molecular clusters were identified for 1980 breast cancer patients. The prognostic significance of the immune-related genes based classification was confirmed in the log-rank test. These clusters were also associated with immune checkpoints, immune-related features and tumor infiltrating levels. In addition, we used the shrunken centroid algorithm to predict the cluster of a given breast cancer sample, and good predictive results were obtained by this algorithm. These results indicated that the proposed classification method is a promising method, and we hope that this method may improve the treatment stratification of breast cancer in the future.

RNA Immune Signatures from Pan-Cancer Analysis Are Prognostic for High-Grade Serous Ovarian Cancer and Other Female Cancers.

Immune cell infiltrates within the tumor microenvironment can influence treatment response and outcome in several cancers. In this study, we developed RNA-based immune signatures from pan-cancer analysis that could serve as potential markers across tumor types and tested them for association with outcome in high-grade serous ovarian cancer (HGSOC) and other female cancers. Pan-cancer RNA-Seq cluster analysis of immune-related gene expression profiles in The Cancer Genome Atlas (TCGA) from 29 different solid tumors (4446 specimens) identified distinct but concordant gene signatures. Among these immune signatures, Cytotoxic Lymphocyte Immune Signature (CLIS), T-cell trafficking (TCT), and the TCT to M2 tumor-associated macrophage (M2TAM) ratio (TCT:M2TAM) were significantly (p < 0.05) associated with overall survival (OS), using multivariable Cox proportional hazards regression models, in a discovery cohort and two independent validation cohorts of HGSOC patients. Notably, the TCT:M2TAM ratio was highly significant (p ≤ 0.000001) in two HGSOC cohorts. Immune signatures were also significant (p < 0.05) in the presence of tumor cytoreduction, BRCA1/2 mutation, and COL2A1 expression. Importantly, the CLIS and TCT signatures were also validated for prognostic significance (p < 0.05) in TCGA cohorts for endometrial and high tumor mutational burden (Hi-TMB) breast cancer. These immune signatures also have the potential for being predictive in other cancers and for patients following different treatment strategies.