The correlation between immune status of patients and their prognosis in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23192-e23192
Author(s):  
Xiao Ding ◽  
Jiuwei Cui ◽  
Xu Yan ◽  
Chao Niu ◽  
Huimin Tian

e23192 Background: In order to investigate the association of immune status with the prognosis in patients with lung cancer and to screen the potential prognostic markers, the immune status including the expression levels of tumor surface molecules, tumor infiltrating lymphocytes (TIL) and cytokines, sMICA and sMICB in serum were detected in this study. Methods: Tissue and serum samples of 125 patients with NSCLC were obtained from the First Hospital of Jilin Universtiy. 50 serum samples of healthy volunteers were obtained as controls. Surface molecules of cancer cell, such as MHC-I, PD-L1, MICA/B and CD8+ TIL were detected with immunohistochemistry. Cytokines such as IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α levels in serum were detected with Luminex. sMICA and sMICB levels were examined by ELISA. The association between their expression levels and patients’ prognosis was analyzed by SPSS 17.0 software. Results: MHC-I was down-expressed, PD-L1 and MICA/B were up-regulated in NSCLC. CD8+ TIL could be seen in tumor stroma and nest. In univariate analysis, we found that patients with down-expression of MHC-I and up-regulation of PD-L1 had a poor prognosis (P < 0.05). MICA/B expression had no correlation with patients’ prognosis (P > 0.05). Patients with more stromal CD8+ TIL might have better prognosis. In multivariate analysis, we found that MHC-I and stromal CD8+ TIL might be independent prognostic factors in NSCLC (P < 0.05). TNF-α and IFN-γ were significantly decreased, IL-6 was increased in NSCLC patients (P < 0.05). There were no connections between the cytokines levels with patients’ prognosis (P > 0.05). Serum sMICA was significantly higher in NSCLC patients than healthy controls (P < 0.05). sMICB tented to be elevated in NSCLC compared with health controls, but there was no significant difference (P > 0.05). High sMICA expression had an association with poor prognosis (P < 0.05). There was no connection between the sMICB level with patients’ prognosis (P > 0.05). Conclusions: The immune status of patients with NSCLC had a close association with their prognosis in this study. It worths further study to confirm the clinical value of MHC-I expression, stromal CD8+ TIL and serum sMICA as prognostic marker in the patients with NSCLC.

2021 ◽  
Vol 8 ◽  
Author(s):  
Humaira Rashid ◽  
Towfida J. Siddiqua ◽  
Biplob Hossain ◽  
Abdullah Siddique ◽  
Mamun Kabir ◽  
...  

Introduction: MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Changes in miRNA expression have been reported in a number of intestinal diseases, in both tissue samples and readily accessible specimens like stools. Pathogenic infections, diet, toxins, and other environmental factors are believed to influence miRNA expression. However, modulation of miRNAs in humans is yet to be thoroughly investigated. In this study, we examined the expression levels of two human miRNAs (miRNA-122 and miRNA-21) in stool samples of a group of Bangladeshi children who had an altered/increased intestinal permeability (IIP).Methods: Stool samples were collected from children with IIP (L:M &gt; 0.09) and normal intestinal permeability (NIP) (L:M ≤ 0.09). Quantitative PCR was performed to quantify the levels of miRNA-122 and miR-21 in stools. Commercial ELISA kits were used to measure gut inflammatory markers Calprotectin and REG1B. Serum samples were tested using Human Bio-Plex Pro Assays to quantify IL-1β, IL-2, IL-5, IL-10, IL-13, IFN-γ, and TNF-α. Total nucleic acid extracted from stool specimens were used to determine gut pathogens using TaqMan Array Card (TAC) system real-time polymerase chain reaction.Results: The expression levels of miRNA-122 (fold change 11.6; p &lt; 0.001, 95% CI: 6.14–11.01) and miR-21 (fold change 10; p &lt; 0.001, 95% CI: 5.05–10.78) in stool were upregulated in children with IIP than in children with normal intestinal permeability (NIP). Significant correlations were observed between stool levels of miR-122 and miR-21 and the inflammatory cytokines IL-1β, IL-2, IFN-γ, and TNF-α (p &lt; 0.05). Children with IIP were frequently infected with rotavirus, Campylobacter jejuni, Bacteroides fragilis, adenovirus, norovirus, astrovirus, and various Escherichia coli strains (ETEC_STh, ETEC_STp, EAEC_aaiC, EAEC_aatA) (p &lt; 0.001). miR-122 significantly correlated with the fecal inflammatory biomarkers REG1B (p = 0.015) and Calprotectin (p = 0.030), however miR-21 did not show any correlation with these fecal biomarkers.


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1306 ◽  
Author(s):  
Ercetin ◽  
Richtmann ◽  
Delgado ◽  
Gomez-Mariano ◽  
Wrenger ◽  
...  

Abstract: High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.


2020 ◽  
Author(s):  
Xinying Li ◽  
Cen Chen ◽  
Zimu Wang ◽  
Jiaxin Liu ◽  
Wei Sun ◽  
...  

Abstract Background: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated with the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. In recent years, many studies have been focusing on the ability of exosomal miRNAs secreted by tumor cells to transmit resistance information. However, the mechanism of exosome-derived miRNAs in osimertinib resistance remains unexplored.Methods: We extracted and sequenced exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975. The results were compared with plasma exosome sequencing before and after the appearance of drug resistance in three NSCLC clinical patients treated with oral osimertinib. Exosome-derived miRNAs that had significantly increased expression levels after osimertinib resistance were screened for expanded validation in other 64 NSCLC patients.Results: Cluster analysis of the target genes revealed that exosomal miRNAs participate in osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality and PI3K pathway activation). Exosome-derived miR-184 (p = 0.0325) and miR-3913-5p (p = 0.0169) expression levels increased significantly after the onset of osimertinib resistance. Exosomal miR-184 was correlated with lactate dehydrogenase levels (p = 0.018). Exosomal miR-3913-5p was associated with TNM stage (p = 0.045), platelet count (p = 0.024), tumor marker carcinoembryonic antigen (p = 0.045), and distant metastases (p = 0.049), especially bone metastasis (p = 0.03). In the subgroup of patients with EGFR exon 21 L858R point mutation, miR-184 (p = 0.0104) and miR-3913-5p (p = 0.0085) derived from serum exosomes had both significantly increased expression levels. In the subgroup of T790M-positive patients, miR-3913-5p derived from serum exosomes may also be a good indicator of osimertinib resistance (p = 0.013).Conclusions: The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of NSCLC patients could be used as biomarkers to indicate osimertinib resistance.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.


2017 ◽  
Vol 39 ◽  
pp. 1-10 ◽  
Author(s):  
R. Balõtšev ◽  
K. Koido ◽  
V. Vasar ◽  
S. Janno ◽  
K. Kriisa ◽  
...  

AbstractBackgroundThere is a growing interest in low-grade inflammatory and metabolic alterations in patients with chronic schizophrenia (SCH).MethodsInflammatory (tumor-necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukins [IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10], monocyte chemo-attractant protein-1 [MCP-1]) and growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF]) were measured in blood serum samples of 105 SCH patients and 148 control subjects (CS). Simultaneously the clinical biomarkers (C-reactive protein [CRP], triglycerides [TG], low-density lipoprotein [LDL-c] and high-density lipoprotein [HDL-c] cholesterol, glycated hemoglobin [HbA1c]) were measured, and body mass index (BMI) was calculated for patients.ResultsSeveral cyto-/chemokines (IFN-γ, MCP-1, IL-2, IL-6, IL-8 and IL-10) were significantly (P < 0.0000001) elevated in SCH patients compared to CS. Odds ratios, obtained from logistic regression analyses, were significantly elevated for IL-2, IL-6, IL-10, INF-γ, and decreased for TNF-α in SCH group. Among the patients, higher IL-2, IL-6, INF-γ and lower MCP-1 levels as well as male gender were together significant (P < 0.000001) predictors of higher HbA1c levels, and TG/HDL-c parameter was associated with ratios of INF-γ/IL-10 (P = 0.004), and INF-γ/IL-4 (P = 0.049), HbA1c (P = 0.005), INF-γ (P = 0.009), as well as LDL-c (P = 0.02) levels.ConclusionsIL-2, IL-6, IL-10 and IFN-γ were the most significant SCH-related markers among the measured cytokines in our patient group. Furthermore, significant associations between pro-/anti-inflammatory imbalance and HbA1c as well as cardio-metabolic risk marker (TG/HDL-c) were observed, indicating higher risks of diabetes and cardiovascular diseases among SCH patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Francesco Grossi ◽  
Maria Giovanna Dal Bello ◽  
Sandra Salvi ◽  
Roberto Puzone ◽  
Ulrich Pfeffer ◽  
...  

Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class IIIbeta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5432 ◽  
Author(s):  
Wen-Ta Li ◽  
Lei-Ya Wang ◽  
Hui-Wen Chang ◽  
Wei-Cheng Yang ◽  
Chieh Lo ◽  
...  

Background Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic levels, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types: Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-γ/Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods Blood samples were collected from six captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 µg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 µg/ml C-AgNP20 treatment. At 24 h of culture with 1 µg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-γ/IL-4 ratio was significantly decreased at 24 h of culture with 1 µg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 µg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-α was significantly decreased by 1 µg/ml C-AgNP20 after 24 h of culture. Discussion The present study demonstrated that the sublethal dose of C-AgNP20 (≤1 µg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-α. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-α is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.


2021 ◽  
Author(s):  
Jie Zhao ◽  
Wenlu Hang ◽  
Qian Wang ◽  
Yonghong Xu

Abstract Background: Non-small cell lung cancer (NSCLC) is a disease with quite grave prognosis. This study explored the diagnostic efficiency of miR-126-5p and miR-34c-3p in serum extracellular vesicles (EVs) in NSCLC patients.Methods: Serum EVs were extracted from NSCLC patients and healthy people and verified. The expression of miR-126-5p and miR-34c-3p in serum EVs were tested. Correlation of miR-126-5p and miR-34c-3p expression and diagnosis, prognosis and pathological characteristics (age, gender, tumor size, clinical stage, and lymph node metastasis) of NSCLC patients was analyzed. The downstream targets of miR-126-5p and miR-34c-3p were predicted and their roles in diagnosis and prognosis of NSCLC patients were evaluated.Results: miR-126-5p and miR-34c-3p were poorly expressed in serum EVs of NSCLC patients and their low expressions were associated with clinical stage, lymph node metastasis and prognosis of NSCLC patients and could be used as biomarkers for diagnosis. As the common target genes of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 were highly expressed in serum EVs and were associated with poor prognosis in NSCLC patients.Conclusion: Lowly expressed miR-126-5p and miR-34c-3p in serum EVs of NSCLC patients can serve as biomarkers for diagnosis and are linked with prognosis. As common targets of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 are also associated with poor prognosis in NSCLC patients.


Sign in / Sign up

Export Citation Format

Share Document