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Li W, Huang X, Han X, Zhang J, Gao L, Chen H. IL-17A in gastric carcinogenesis: good or bad? Front Immunol 2024; 15:1501293. [PMID: 39676857 PMCID: PMC11638189 DOI: 10.3389/fimmu.2024.1501293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 11/13/2024] [Indexed: 12/17/2024] Open
Abstract
Cytokines, which are important to the tumor microenvironment (TME), play critical roles in tumor development, metastasis, and immune responses. Interleukin-17(IL-17) has emerged as a key biomarker in many malignancies; however, its precise involvement in gastric cancer is less fully understood. Elevated levels of IL-17 have been observed in stomach diseases such as Helicobacter pylori infection and autoimmune gastritis, indicating that a sustained Th17 response may precede the development of gastric cancer. While IL-17 is related to inflammatory processes that may lead to cancer, its specific influence on gastric cancer development and therapy needs to be completely understood. Specifically, the release of IL-17A by diverse immune cells has been associated with both tumor development and inhibition in gastric cancer. It may impact tumor development through mechanisms such as boosting cell proliferation, inducing angiogenesis, and enabling immune cell recruitment or, conversely, suppressing tumor growth via the activation of anti-tumor immune responses. The dual role of IL-17 in cancer, along with its various effects depending on the TME and immune cell composition, highlights the complexity of its activity. Current research reveals that although IL-17 might serve as a target for immunotherapy, its therapeutic potential is hindered by its various activities. Some studies have shown that anti-IL-17 drugs may be helpful, especially when paired with immune checkpoint inhibitors, whereas others point to concerns about the validity of IL-17 in gastric cancer therapy. The lack of clinical trials and the heterogeneity of human tumors underscore the necessity for individualized treatment approaches. Further studies are needed to identify the specific mechanisms of IL-17 in gastric cancer and to design targeted therapeutics appropriately.
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Affiliation(s)
- Weidong Li
- Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaodong Huang
- Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaowen Han
- Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China
| | - Jiayi Zhang
- Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China
| | - Lei Gao
- Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China
| | - Hao Chen
- Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China
- Key Laboratory of Environmental Oncology of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China
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Sadafi S, Amirifard N, Aleagha OE, Mirbahari SG, Sadeghi M. A Meta-Analysis of Association Between Interleukin Polymorphisms (rs4073, rs1800925, rs1179251, rs1179246, rs2227485, rs17855750, and rs153109) and Colorectal Cancer Risk. Biochem Genet 2024:10.1007/s10528-024-10969-1. [PMID: 39548028 DOI: 10.1007/s10528-024-10969-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 11/01/2024] [Indexed: 11/17/2024]
Abstract
Interleukins (ILs) play a significant role in triggering the inflammatory response in blood vessels and immune cells. A systematic review and meta-analysis were conducted to investigate the relationship between IL-8 (rs4073), IL-13 (rs1800925), IL-22 (rs1179251, rs1179246, and rs2227485), and IL-27 (rs17855750 and rs153109) polymorphisms and the risk of developing colorectal cancer (CRC). Four databases were searched up until October 13, 2023, without any restrictions, to find relevant studies. The association was evaluated using crude odds ratios (ORs) and 95% confidence intervals in five genetic models. A total of twenty-three articles were entered into the meta-analysis. The pooled ORs (p-values) for the IL-8 (rs4073) polymorphism were 0.98 (0.63), 0.93 (0.44), 0.89 (0.13), 0.94 (0.38), and 0.99 (0.90) for studies following HWE without heterogeneity, and for all studies with high heterogeneity were 1.03 (0.69), 1.30 (0.07), 1.04 (0.71), 1.12 (0.20), and 1.23 (0.06). For the IL-13 (rs1800925) polymorphism, the pooled ORs were 1.44 (0.06), 2.58 (0.0004), 1.72 (0.16), 1.82 (0.09), and 2.37 (0.001) in AHHDR models, respectively. The pooled ORs of IL-22 (rs1179251) polymorphism for AHHDR models were 0.97 (0.92), 0.92 (0.90), 0.98 (p = 0.95), 1.08 (0.87), and 0.96 (0.82), respectively. The pooled ORs of IL-22 (rs1179246) polymorphism for AHHDR models were 0.98 (0.67), 0.97 (0.80), 0.92 (0.36), 0.93 (0.42), and 1.02 (0.84), respectively. The pooled ORs of IL-22 (rs2227485) polymorphism for AHHDR models were 1.47 (0.02), 2.03 (0.02), 1.28 (0.29), 1.52 (0.06), and 1.70 (0.04), respectively. The pooled ORs of IL-27 (rs17855750) polymorphism for AHHDR models were 0.53 (0.46), 0.19 (0.28), 1.10 (0.60), 0.55 (0.58), and 0.27 (p = 0.05), respectively. The pooled ORs of IL-27 (rs153109) polymorphism for AHHDR models were 1.28 (0.007), 1.45 (0.002), 1.40 (0.0002), 1.41 (< 0.0001), and 1.20 (0.09), respectively. The results reported that just the TT genotype of IL-13 (rs1800925), the T allele and TT genotype of IL-22 (rs2227485), and the G allele and GG, AG and GG + AG genotypes of IL-27 (rs153109) polymorphisms had an elevated risk in CRC patients.
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Affiliation(s)
- Sepehr Sadafi
- Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nasrin Amirifard
- Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Omid Emami Aleagha
- Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seyed Ghasem Mirbahari
- Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Jam Private Medical Laboratory, Kermanshah, Iran.
| | - Masoud Sadeghi
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Alsayed BA, Mir R, Mir MM, Alnour TM, Fawzy S, M. Ahmed M, Amle D. Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients. Curr Genomics 2024; 25:12-25. [PMID: 38544825 PMCID: PMC10964085 DOI: 10.2174/0113892029272497240103052359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 12/04/2023] [Accepted: 12/20/2023] [Indexed: 08/25/2024] Open
Abstract
Background Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.
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Affiliation(s)
- Badr A. Alsayed
- Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Saudi Arabia
| | - Rashid Mir
- Department of Medical Lab technology Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, 71491, Saudi Arabia
| | - Mohammad M. Mir
- Department of Basic Medical Sciences (Biochemistry), College of Medicine, University of Bisha, Bisha, 61922, Saudi Arabia
| | - Tarig M.S. Alnour
- Department of Medical Lab technology Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, 71491, Saudi Arabia
| | - Shereen Fawzy
- Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Saudi Arabia
| | - Mesaik M. Ahmed
- Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, 71491, Saudi Arabia
| | - Dnyanesh Amle
- Department of Biochemistry, All India Institute of Medical Sciences, Nagpur, 441108, India
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Yang WJ, Zhao HP, Yu Y, Wang JH, Guo L, Liu JY, Pu J, Lv J. Updates on global epidemiology, risk and prognostic factors of gastric cancer. World J Gastroenterol 2023; 29:2452-2468. [PMID: 37179585 PMCID: PMC10167900 DOI: 10.3748/wjg.v29.i16.2452] [Citation(s) in RCA: 158] [Impact Index Per Article: 79.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/19/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.
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Affiliation(s)
- Wen-Juan Yang
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China
| | - Lei Guo
- Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Jun-Ye Liu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Jie Pu
- Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi'an 710068, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
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Association of IL-8-251T/A (rs4073) gene polymorphism with Systemic lupus erythematosus in a cohort of Egyptian patients. Int Immunopharmacol 2023; 114:109528. [PMID: 36481529 DOI: 10.1016/j.intimp.2022.109528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/27/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Systemic lupus erythematosus (SLE) susceptibility was found to be correlated with genetic polymorphisms. Therefore, the current study aimed to investigate the association of the IL-8-251 T/A polymorphism with the risk of SLE. METHODS A total of 135 SLE patients and 75 controls were enrolled in our study. The IL-8-251 T/A polymorphism was analysed by PCR-RFLP. Also, the serum concentration of IL-8 was measured using ELISA. Finally, investigate possible IL-8 pathways in SLE pathogenesis by using the STRING database. RESULTS Our results revealed that the risk of having SLE in AA genotype carriers was significantly increased (OR = 1.92, 95 % CI = 1.23-3.10, p = 0.006) when compared with TT genotype carriers. Patients with SLE had a significantly higher frequency of the A allele (OR = 1.37, 95 % CI = 1.09-1.7; P = 0.01) than controls. Serum IL-8 levels were significantly increased in SLE patients (77.81 ± 21.27; p < 0.001) when compared to healthy controls (48.85 ± 7.89). Also, it was found that the serum IL-8 level had significant positive correlations with proteinuria, ESR, ANA, urea and SELADI, and significant negative correlations with RBCs count, C3 and hemoglobin. According to ROC curve analysis, serum IL-8 levels are a good biomarker for the detection of SLE disease, with 87.5 % sensitivity and 85 % specificity. STRING analysis revealed that IL-8 interacts with key SLE signaling pathway members such as TNF-α, IL-1β, IL-6, and IL-10. CONCLUSIONS There was a correlation between the IL-8-251 T/A polymorphism and the risk of SLE. Our findings also suggest that the IL8-251 A allele may be an important risk factor for the development of SLE.
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Lyu Y, Yang S, Lyu X, Wang YL, Ji S, Kang S, Jiang Y, Xiang J, He C, Li P, Liu B, Wu C. lncRNA polymorphism affects the prognosis of gastric cancer. World J Surg Oncol 2022; 20:273. [PMID: 36045445 PMCID: PMC9429416 DOI: 10.1186/s12957-022-02723-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 08/06/2022] [Indexed: 11/20/2022] Open
Abstract
Background Previous studies have found that lncRNA polymorphisms are associated with the prognosis of gastric cancer (GC), but the specific roles of many lncRNA polymorphism sites in gastric cancer are still unclear. Our study aims to deeply explore the relationship between genetic polymorphism of lncRNA and the prognosis of GC. Methods The genotypes of candidate SNP locus were detected by Sequenom Mass ARRAY SNP. We deeply analyzed the association of lncRNA polymorphisms with GC prognosis by univariate and multivariate Cox regression, stratified analysis, conjoint analysis, and log-rank test. Results We found that mutations at rs2579878 and rs10036719 loci reduced the risk of poor prognosis of GC. Stratified analysis showed that rs2795025, rs10036719, and rs12516079 polymorphisms were all associated with tumor prognosis. In addition, conjoint analyses showed that the interaction between these two polymorphic sites (rs2795025 and rs12516079) could increase the risk of poor prognosis. Multivariate analysis also found that the AG/AA genotype of rs10036719 and AG genotype of rs12516079 were independent prognostic factors. Moreover, the high expression of both CCDC26 and LINC02122 were shown to be associated with the poor survival status of GC patients. Conclusions We find that the genetic polymorphism of lncRNA plays a role in the development of GC and is closely related to the survival time of patients. It could serve as a predictor of the prognosis of GC.
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Affiliation(s)
- Yanping Lyu
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Shuangfeng Yang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Xuejie Lyu
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Yuan-Liang Wang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Shumi Ji
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Shuling Kang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China.,Fuzhou Center for Disease Control and Prevention, Fuzhou, China
| | - Yu Jiang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Jianjun Xiang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Chenzhou He
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Peixin Li
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Baoying Liu
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China. .,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China.
| | - Chuancheng Wu
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China. .,The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, China.
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Cerrato-Izaguirre D, Chirino YI, García-Cuellar CM, Santibáñez-Andrade M, Prada D, Hernández-Guerrero A, Larraga OA, Camacho J, Sánchez-Pérez Y. Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine. Genes Dis 2022; 9:928-940. [PMID: 35685475 PMCID: PMC9170608 DOI: 10.1016/j.gendis.2021.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 04/01/2021] [Indexed: 02/07/2023] Open
Abstract
Latin-America (LATAM) is the second region in gastric cancer incidence; gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian; IL-10 in Chilean; IL-10 in Colombian; EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.
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Affiliation(s)
- Dennis Cerrato-Izaguirre
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV), Ciudad de México, CP 07360, Mexico
| | - Yolanda I. Chirino
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, Tlalnepantla de Baz, Estado de México, CP 54090, Mexico
| | - Claudia M. García-Cuellar
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Miguel Santibáñez-Andrade
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Diddier Prada
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
- Departamento de Informática Biomédica, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, CP 04510, Mexico
- Department of Environmental Health Science, Mailman School of Public Health, Columbia University, New York, NY 10027, USA
| | - Angélica Hernández-Guerrero
- Servicio de Endoscopía, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Octavio Alonso Larraga
- Servicio de Endoscopía, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
| | - Javier Camacho
- Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV), Ciudad de México, CP 07360, Mexico
| | - Yesennia Sánchez-Pérez
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Tlalpan, Ciudad de México, CP 14080, Mexico
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8
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The association between single polymorphic positions and the risk of acute lymphoblastic leukemia. Meta Gene 2022. [DOI: 10.1016/j.mgene.2021.101006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Yin HH, Xu MQ, Liu BZ, Tao L, Ma YJ, Li F, Zhang WJ. Combination of preoperative CA19-9 levels, cell differentiation, and age predicts survival for patients with gastric cancer before surgery. Medicine (Baltimore) 2021; 100:e28017. [PMID: 34889247 PMCID: PMC8663841 DOI: 10.1097/md.0000000000028017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 11/11/2021] [Indexed: 01/05/2023] Open
Abstract
Gastric cancer (GC) is very common in China, posing a threat to public health, with high morbidity and mortality ranks. Tumor-node-metastasis (TNM) staging system is routinely used to predict prognosis for patients with GC but only available after surgery. Therefore, searching for markers that can predict prognosis of GC patients before surgery is desirable to assist management decisions preoperatively. Among 322 GC patients followed-up for 128 months, the tumor markers alpha fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 and carbohydrate antigen 72-4 of 168 patients were detected before surgery, and their impact on survival was analyzed. Four major findings were revealed: (1) Preoperative examined CA19-9 levels and cell differentiation using endoscopic biopsies were positively correlated with lymphatic metastases and TNM stages obtained after surgery. (2) Kaplan-Meier analyses demonstrated that poor survival of patients with GC was associated with higher CA19-9 levels, poor cell differentiation, and older age. (3) Cox multi-factorial regression analyses indicated that, in terms of predicting overall survival for GC patients, preoperative CA19-9 level, cell differentiation and age were independent factors, respectively, comparable to postoperative TNM staging system. (4) Using receiver operating characteristic curve analysis, we first revealed that preoperative CA19-9 levels and cell differentiation had the impact weights (IW) on survival comparable to postoperative TNM components. These findings suggest that preoperative CA19-9 levels, cell differentiation and age are useful prognostic related markers for GC patients, superior to postoperative TNM system in terms of timing for management. We propose that, assisted by clinical imaging, a comprehensive utilization of these preoperative survival-predictors may help formulate individualized medical management for GC patients such as surgical strategy, optimal chemotherapy and radiotherapy, and appropriate follow-up intervals after surgery.
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Affiliation(s)
- Hui Hui Yin
- Department of Pathology, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- Department of Pathology, Wuxi Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine/Xinrui Hospital of Xinwu District, Wuxi, Jiangsu, China
| | - Meng Qing Xu
- Department of Pathology, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- Department of Gastroenterology, Jinling Hospital, Nanjing, Jiangsu, China
| | - Bin Zheng Liu
- Department of Pathology, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Lin Tao
- Department of Pathology, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Ya Jing Ma
- Department of Clinical Laboratories, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Feng Li
- Department of Pathology, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- Department of Pathology, Beijing Chaoyang Hospital, the Capital Medical University, Beijing, China
| | - Wen Jie Zhang
- Department of Pathology, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
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10
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Torricelli C, Carron J, Carvalho BF, Macedo LT, Rinck-Junior JA, Lima CSP, Lourenço GJ. Influence of IL1B (rs16944) and IL1R2 (rs4141134) polymorphisms on aggressiveness and prognosis of cutaneous melanoma. Melanoma Res 2021; 31:476-481. [PMID: 34284461 DOI: 10.1097/cmr.0000000000000763] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Cutaneous melanoma is the most aggressive skin cancer with high mortality. Proinflammatory cytokines can modulate the proliferation and survival of cutaneous melanoma cells. Higher levels of interleukin-1β (IL1B) were associated with tumor cell proliferation, invasion, and migration, and the IL-1 type II receptor (IL1R2) serves as an endogenous inhibitor of IL1B signaling. Single-nucleotide variations (SNVs) in these genes (IL1B rs16944 and IL1R2 rs4141134) can modulate cytokine production and binding; however, their role in cutaneous melanoma is still unknown. Thus, we investigated the influence of the above SNVs in clinicopathological aspects and cutaneous melanoma patients' survival. In the present study, we analyzed 193 patients with cutaneous melanoma for IL1B c.-598T>C (rs16944) and IL1R2 c.-2009G>A (rs4141134) genotypes with TaqMan assays. Differences between groups were calculated using χ2 or Fisher's exact test and multiple logistic regression. Progression-free survival (PFS) and melanoma-specific survival were calculated by Kaplan-Meier and Cox methods. The prognostic value of IL1R2 was also analyzed by the online consensus survival webserver for skin cutaneous melanoma (OSskcm). We found that IL1R2 rs4141134 GG genotype was more common in patients with nodular subtype (49.1% vs. 29.8%, P = 0.01) and the frequency of IL1R2 rs4141134 GG or GA was higher in patients with Clark levels III-V (87.4% vs. 75.8%, P = 0.04). Patients with IL1R2 rs4141134 GG or GA genotypes presented lower PFS (hazard ratio: 3.12, 95% confidence interval, 1.10-8.79, P = 0.03) when compared with AA genotype, supported by OSskcm results. Thus, our study presented for the first time preliminary evidence that IL1R2 rs4141134 SNV may modulate cutaneous melanoma clinicopathological aspects and survival possible by allowing IL1B signaling.
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Affiliation(s)
- Caroline Torricelli
- Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas
| | - Juliana Carron
- Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas
| | | | - Ligia Traldi Macedo
- Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas
- Clinical Oncology Service, Department of Radiology, School of Medical Sciences, University of Campinas
| | | | - Carmen Silvia Passos Lima
- Laboratory of Cancer Genetics, School of Medical Sciences, University of Campinas
- Clinical Oncology Service, Department of Radiology, School of Medical Sciences, University of Campinas
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11
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Wang Z, Hou Y, Yao Z, Zhan Y, Chen W, Liu Y. Expressivity of Interleukin-8 and Gastric Cancer Prognosis Susceptibility: A Systematic Review and Meta-Analysis. Dose Response 2021; 19:15593258211037127. [PMID: 34531708 PMCID: PMC8438942 DOI: 10.1177/15593258211037127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/07/2021] [Accepted: 07/09/2021] [Indexed: 12/23/2022] Open
Abstract
Background The relationship between interleukin-8 (IL-8) expression and the prognosis of gastric cancer (GC) patients has been reported, but the results are contradictory. Aim To investigate the effect of IL-8 expression on the prognosis of patients with GC. Method A comprehensive search strategy was used to search the PubMed, Web of Science and Cochrane Library databases. The total survival time was analysed using the RevMan 5.4 software. Through extensive search and meta-analysis of relevant studies, studies examining the relationship between IL-8 expression and prognosis in patients with GC were conducted to obtain more accurate estimates. Findings Eight studies (1843 patients) were included. The combined results of all the studies showed that high expression of IL-8 was a risk factor for poor prognosis in patients with GC (hazard ratio (HR): 2.08; 95% CI: 1.81–2.39). Sensitivity analysis suggested that the pooled HR was stable, and omitting a single study did not change the significance of the pooled HR. Funnel plots revealed no significant publication bias in the meta-analysis. Conclusion High IL-8 expression could be a negative prognostic biomarker for patients with GC.
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Affiliation(s)
- Zhenzhen Wang
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuhan Hou
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhen Yao
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yanyan Zhan
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Wenyue Chen
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yulong Liu
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China.,State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.,Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, China
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12
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Impact of interleukin-32 germ-line rs28372698 and intronic rs12934561 polymorphisms on cancer development: A systematic review and meta-analysis. Int Immunopharmacol 2021; 99:107964. [PMID: 34271417 DOI: 10.1016/j.intimp.2021.107964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/21/2021] [Accepted: 07/05/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVE The pro-inflammatory cytokine IL-32 has high susceptibility to develop cancer. But no previous meta-analysis was done to provide firm evidence. This systematic review and meta-analysis was designed to evaluate the association of IL-32 gene polymorphisms (rs28372698 and rs12934561) with cancer. METHOD Eligible studies were selected using authentic databases searching from January 2013 to January 2021. Demographic data and genotypic information were extracted and organized from the selected studies. Review Manager (RevMan) version 5.4 was used to perform data analysis and data arrangement for meta-analysis. RESULTS A total of seven studies with 3395 patients and 3781 controls were included in this study. IL-32 rs28372698 polymorphism implied that mutant allele (TT) carriers had a significantly higher risk of cancer (OR = 1.43, p = 0.032). Codominant 3, recessive and allele models also showed 1.36-, 1.38- and 1.11-fold increased risk, respectively (p < 0.05). Besides, the Asian population showed a significantly increased risk in codominant 2 (OR = 1.74), codominant 3 (OR = 1.78), recessive (OR = 1.76) and allele model (OR = 1.16). IL-32 rs12934561 showed significantly reduced cancer risk in codominant 1 (OR = 0.66. p = 0.035), codominant 2 (OR = 0.76, p = 0.007), and dominant model (OR = 0.72, p = 0.012). After subgroup analysis, an association of rs12934561 was found in Asians (codominant 1: OR = 0.54, p = 7.28 × 10-8; codominant 2: OR = 1.40, p = 0.019; codominant 3: OR = 0.76, p = 0.0006; dominant model: OR = 0.64, p = 1.12 × 10-5; overdominant model: OR = 0.64, p = 3.92 × 10-7) but not in Caucasians. After stratifying with the control source, a significant (p < 0.05) association of rs28372698 and rs12934561 was found with cancer in population-based controls. No publication bias was found, and the outcome of this meta-analysis was not influenced by any individual study confirmed from sensitivity analysis. Moreover, trial sequential analysis (TSA) established a link between rs28372698 and rs12934561 polymorphisms and cancer. CONCLUSION The outcome of this meta-analysis revealed that IL-32 rs28372698 and rs12934561 polymorphisms are associated with cancer. Moreover, the Asian dynasty had a significant association compared to Caucasians.
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Paximadis M, Picton ACP, Sengupta D, Ramsay M, Puren A, Tiemessen CT. Interleukin-8 genetic diversity, haplotype structure and production differ in two ethnically distinct South African populations. Cytokine 2021; 143:155489. [PMID: 33814271 DOI: 10.1016/j.cyto.2021.155489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 10/14/2020] [Accepted: 02/28/2021] [Indexed: 11/16/2022]
Abstract
A single nucleotide polymorphism (SNP), 251 bases upstream from the IL-8 transcription start (-251A>T, rs4073), has been extensively investigated in cancers and inflammatory and infectious diseases in predominantly European and Asian populations. We sequenced the IL-8 gene of 109 black and 32 white South African (SA) individuals and conducted detailed characterization of gene variation and haplotype structure. IL-8 production in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) of a subset (black: N = 22; white: N = 32) of these individuals was measured using ELISA. Select variants were genotyped for additional black individuals (N = 141), and data from the 1000 Genomes Project were used for haplotype analysis and comparative purposes. In white individuals, the -251A>T SNP formed part of a prevalent six-variant haplotype [haplotype frequency (HF): 61%], Hap-1C, involving the following variants: -251A>T; +394T>G (rs2227307); +780C>T (rs2227306); +1240->A (rs2227541); +1635C>T (rs2227543) and +2770A>T (rs2227543). Hap-1C (-251T+394T+780C+1240+A+1635C+2770A) was composed of two three-variant sub-haplotypes [Hap-1Ca: -251T+394T+1240+A; Hap-1Cb: +780C+1635C+2770A) sharing similarities with haplotypes identified in the black population. Hap-1C was found to be present in European, East and South Asian populations. Four haplotypes were identified in the black population with the two prevalent haplotypes each comprised of two variants: Hap-1B [-251A>T and +1240->A; -251T+1240+A; HF: 14%] and Hap-2B [-743T>C (rs2227532) and +2452A>C (rs2227545); -743C+2452C; HF: 13%]. Populations did not differ in unstimulated PBMC IL-8 production. Upon PHA stimulation, PBMCs from white individuals produced more IL-8 (P = 0.04), suggesting the -251T allele is responsible for higher production, however further analysis revealed that Hap-1C (and constituent sub-haplotypes), did not associate with IL-8 production. Populations did however differ in monocyte number with the white population having significantly more monocytes compared to the black population (P = 0.025), and furthermore monocyte number strongly correlated with IL-8 production in both population groups (black: p = 0.0002, r = 0.71; white: P = 0.0005, r = 0.59). Hap-1B, Hap-2B, and a SNP located one base pair upstream of the IL-8 ATG start codon, +100C>T SNP (rs2227538), all associated with higher IL-8 production in the black population - individuals harbouring at least one of these haplotypes/variant associated with higher IL-8 production (P = 0.003) compared to individuals without. The black population was enriched for individuals harbouring Hap-1B and/or Hap-2B compared to the 1000 Genomes project sub-Saharan African population (P = 0.006), suggesting that SA black individuals may be high IL-8 producers. Given the paucity of IL-8-related studies that have been conducted in populations from sub-Saharan Africa, this study has significantly increased our understanding of this important chemokine in the South African population.
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Affiliation(s)
- Maria Paximadis
- Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Anabela C P Picton
- Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Dhriti Sengupta
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Michele Ramsay
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Adrian Puren
- Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Caroline T Tiemessen
- Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Grolmusz VK, Bozsik A, Papp J, Patócs A. Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification. Front Immunol 2021; 12:653489. [PMID: 33763088 PMCID: PMC7982482 DOI: 10.3389/fimmu.2021.653489] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 02/16/2021] [Indexed: 12/15/2022] Open
Abstract
The ongoing COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2 has affected all aspects of human society with a special focus on healthcare. Although older patients with preexisting chronic illnesses are more prone to develop severe complications, younger, healthy individuals might also exhibit serious manifestations. Previous studies directed to detect genetic susceptibility factors for earlier epidemics have provided evidence of certain protective variations. Following SARS-CoV-2 exposure, viral entry into cells followed by recognition and response by the innate immunity are key determinants of COVID-19 development. In the present review our aim was to conduct a thorough review of the literature on the role of single nucleotide polymorphisms (SNPs) as key agents affecting the viral entry of SARS-CoV-2 and innate immunity. Several SNPs within the scope of our approach were found to alter susceptibility to various bacterial and viral infections. Additionally, a multitude of studies confirmed genetic associations between the analyzed genes and autoimmune diseases, underlining the versatile immune consequences of these variants. Based on confirmed associations it is highly plausible that the SNPs affecting viral entry and innate immunity might confer altered susceptibility to SARS-CoV-2 infection and its complex clinical consequences. Anticipating several COVID-19 genomic susceptibility loci based on the ongoing genome wide association studies, our review also proposes that a well-established polygenic risk score would be able to clinically leverage the acquired knowledge.
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Affiliation(s)
- Vince Kornél Grolmusz
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
- Hereditary Tumors Research Group, Eötvös Loránd Research Network—Semmelweis University, Budapest, Hungary
| | - Anikó Bozsik
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
- Hereditary Tumors Research Group, Eötvös Loránd Research Network—Semmelweis University, Budapest, Hungary
| | - János Papp
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
- Hereditary Tumors Research Group, Eötvös Loránd Research Network—Semmelweis University, Budapest, Hungary
| | - Attila Patócs
- Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
- Hereditary Tumors Research Group, Eötvös Loránd Research Network—Semmelweis University, Budapest, Hungary
- Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
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Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma. Cancers (Basel) 2021; 13:cancers13030529. [PMID: 33573284 PMCID: PMC7866803 DOI: 10.3390/cancers13030529] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 01/26/2021] [Accepted: 01/27/2021] [Indexed: 01/21/2023] Open
Abstract
Simple Summary Neuroblastoma (NB) presents diverse biological and clinical characteristics, from spontaneous regression to highly malignant and aggressive unfavorable tumors that condition the therapeutic failure of conventional treatments. The tumorigenesis of NB can be the result of different genetic variants, which can influence the clinical outcome, and the survival of patients who have metastatic tumors is low. The role of cytokines such as interleukin (IL)-6 has been described in the NB microenvironment promoting tumor progression and metastasis. Single nucleotide polymorphism (SNP)-174 G > C in IL-6 and -251 T > A and +781 C > T in IL-8 regulate the expression of these cytokines, and could be associated with the clinical outcome in patients with NB. Our objective was to evaluate the association of the genetic polymorphisms of IL-6 and IL-8, as well as the serum levels of these cytokines in patients with NB, as this will allow the genetic bases of NB to be characterized and understood, in order to predict the outcome of the disease and develop new therapeutic strategies. Abstract There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.
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Miller H, Czigany Z, Lurje I, Reichelt S, Bednarsch J, Strnad P, Trautwein C, Roderburg C, Tacke F, Gaisa NT, Knüchel-Clarke R, Neumann UP, Lurje G. Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection. Cancers (Basel) 2020; 12:cancers12123826. [PMID: 33352897 PMCID: PMC7767259 DOI: 10.3390/cancers12123826] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/13/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma remains a leading cause of cancer-related death and the most common primary hepatic malignancy in the Western hemisphere. Previous research found that angiogenesis-related cytokines and elevated levels of interleukin 8 and vascular endothelial growth factor (VEGF) shorten the expected time of survival. Moreover, factors of tumor angiogenesis- and hypoxia-driven signaling pathways are already associated with worse outcome in disease-free survival in several tumor entities. Our study investigates the prognosis of hepatocellular carcinoma patients based on a selection of ten different single-nucleotide polymorphisms from angiogenesis, carcinogenesis, and hypoxia pathways. Our study with 127 patients found supporting evidence that polymorphisms in angiogenesis-associated pathways corelate with disease-free survival and clinical outcome in patients with hepatocellular carcinoma. Abstract Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)–restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of “high-expression” variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients’ individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.
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Affiliation(s)
- Hannah Miller
- Charité–Universitätsmedizin Berlin, Department of Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany; (H.M.); (S.R.)
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
| | - Isabella Lurje
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
- Charité–Universitätsmedizin Berlin, Department of Gastroenterology and Hepatology, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany; (C.R.); (F.T.)
| | - Sophie Reichelt
- Charité–Universitätsmedizin Berlin, Department of Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany; (H.M.); (S.R.)
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (P.S.); (C.T.)
| | - Christian Trautwein
- Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (P.S.); (C.T.)
| | - Christoph Roderburg
- Charité–Universitätsmedizin Berlin, Department of Gastroenterology and Hepatology, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany; (C.R.); (F.T.)
- Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (P.S.); (C.T.)
| | - Frank Tacke
- Charité–Universitätsmedizin Berlin, Department of Gastroenterology and Hepatology, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany; (C.R.); (F.T.)
- Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (P.S.); (C.T.)
| | - Nadine Therese Gaisa
- Institute of Pathology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (N.T.G.); (R.K.-C.)
| | - Ruth Knüchel-Clarke
- Institute of Pathology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (N.T.G.); (R.K.-C.)
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
| | - Georg Lurje
- Charité–Universitätsmedizin Berlin, Department of Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany; (H.M.); (S.R.)
- Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany; (Z.C.); (I.L.); (J.B.); (U.P.N.)
- Correspondence: ; Tel.: +49-30-450-652339
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Althubyani SA, Alkhuriji AF, Al Omar SY, El-Khadragy MF. A preliminary study of cytokine gene polymorphism effects on Saudi patients with colorectal cancer. Saudi Med J 2020; 41:1292-1300. [PMID: 33294886 PMCID: PMC7841582 DOI: 10.15537/smj.2020.12.25543] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 11/01/2020] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To determine the possible associations of polymorphisms in interleukin (IL)-8 (rs4073 T/A), IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G and rs2227485 C/T), IL-27 (rs17855750 T/G), and transforming growth factor beta 1 (TGFß1) (rs1800469 C/T) with colorectal cancer (CRC) susceptibility in Saudi patients. METHODS The case-control study was carried out between July 2019 and January 2020 in King Khaled University Hospital, Riyadh, Saudi Arabia. A total of 70 patients with CRC and 70 healthy controls were included in the study. Single nucleotide polymorphisms of promoter regions were determined using TaqMan genotyping assays. RESULTS A statistically significant reduction in CRC risk was identified for carriers of the IL-10 (rs1800896 A/G) AG genotype, IL-22 (rs1179251 C/G) G allele, IL-27 (rs17855750 T/G) G allele and TGFß1 (rs1800469 C/T) CT and TT genotype. While IL-10 (rs1800896 A/G) AA genotype and TGFß1 (rs1800469 C/T) CC genotype were significantly associated with increased susceptibility to CRC. No significant associations were identified between the cytokine polymorphisms of IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T), and CRC risk. Conclusion: Our findings indicate a significant impact of IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G), IL-27 (rs17855750 T/G) and TGF-ß1 (rs1800469 C/T) polymorphisms on risk of CRC; while the IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T) and polymorphisms were not associated with CRC risk.
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Affiliation(s)
- Sarah A Althubyani
- Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.
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Associations between Interleukin-32 Gene Polymorphisms rs12934561 and rs28372698 and Susceptibilities to Bladder Cancer and the Prognosis in Chinese Han Population. DISEASE MARKERS 2020; 2020:8860445. [PMID: 33204366 PMCID: PMC7661138 DOI: 10.1155/2020/8860445] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/20/2020] [Accepted: 10/24/2020] [Indexed: 02/05/2023]
Abstract
The proinflammatory chemokine interleukin-32 is related to various diseases, including cancer. However, it has never been associated with bladder cancer (BC). To detect whether there is a relationship between the IL-32 gene polymorphisms (rs12934561 C/T and rs28372698 T/A) and BC, the study enrolled 170 non-muscle-invasive bladder cancer (NMIBC) patients, 151 muscle-invasive bladder cancer (MIBC) patients, and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the IL-32 single-nucleotide polymorphism (SNP) genotyping. Statistical analysis was performed using SNPstats online analysis software and SPSS software. Our data revealed that the CC homozygous genotype of rs12934561 in BC patients was significantly higher than that in controls (P = 0.03, OR = 1.47, 95%CI = 1.04‐2.08), and the percentage of TC genotype carriers was relatively less than that of controls (P = 0.001, OR = 0.61, 95%CI = 0.45‐0.82). Furthermore, the TT homozygous genotype of rs28372698 was associated with a significantly lower overall survival rate in MIBC patients (P = 0.028, OR = 2.77, 95%CI = 1.11‐6.90). The IL-32 gene polymorphism rs12934561 might be associated with increased BC risk, and the rs28372698 might participate in the prognosis of BC patients. Therefore, they could be potential forecasting factors for the prognosis of MIBC patients.
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Prediction of gastric cancer risk: association between ZBTB20 genetic variance and gastric cancer risk in Chinese Han population. Biosci Rep 2020; 40:226430. [PMID: 32936247 PMCID: PMC7517264 DOI: 10.1042/bsr20202102] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/19/2020] [Accepted: 09/02/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Gastric cancer (GC) is a complex multifactorial disease. Previous studies have revealed genetic variations associated with the risk of gastric cancer. The purpose of the present study was to determine the correlation between single-nucleotide polymorphisms (SNPs) of ZBTB20 and the risk of gastric cancer in Chinese Han population. Methods: We conducted a ‘case–control’ study involving 509 GC patients and 507 healthy individuals. We selected four SNPs of ZBTB20 (10934270 T/C, rs9288999 G/A, rs9841504 G/C and rs73230612 C/T), and used logistic regression to analyze the relationship between those SNPs and GC risk under different genetic models; multi-factor dimensionality reduction (MDR) was used to analyze the interaction of “SNP–SNP” in gastric cancer risk; ANOVA and univariate analysis were used to analyze the differences in clinical characteristics among different genotypes. Results: Our results showed that ZBTB20 rs9288999 is a protective factor for the risk of gastric cancer in multiple genetic models, of which the homozygous model is the most significant (OR = 0.48, P=0.0003); we also found that rs9288999 showed a significant correlation with reducing the risk of gastric cancer in different subgroups (BMI; age; gender; smoking or drinking status; adenocarcinoma); rs9841504 is associated with increased GC risk in the participants with BMI>24 kg/m2; rs9841504 and rs73230612 are certainly associated with clinical characteristics of platelet and carbohydrate antigen 242, respectively. Conclusion: Our results suggest that ZBTB20 rs9288999 may be important for reducing the risk of GC in the Chinese Han population.
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Liu L, Zhai Z, Wang D, Ding Y, Chen X, Wang Q, Shu Z, Wu M, Chen L, He X, Fan D, Pan F, Xing M. The association between IL-1 family gene polymorphisms and colorectal cancer: A meta-analysis. Gene 2020; 769:145187. [PMID: 32998046 DOI: 10.1016/j.gene.2020.145187] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 07/26/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is a major public health problem given its high incidence and mortality. This study focuses on examining the associations between IL-1α, IL-1β, and IL-1RN polymorphisms and colorectal cancer susceptibility. METHODS A systematic literature search of PubMed, Embase, Web of Science, CNKI (China National Knowledge Infrastructure) and Wan Fang databases was conducted to identify relevant studies. Relevant data were extracted from the original included studies. The correlation was demonstrated based on the odds ratio (OR) and corresponding 95% confidence intervals (95% CIs). Publication bias was investigated by Egger's line regression test and Begg's funnel plot. RESULTS Eighteen independent studies involving 6218 cases and 10160 controls were eligible for this pooled analysis. Overall, the result revealed that the IL-1α rs3783553 polymorphism was significantly associated with an increased risk of CRC (G vs. C, OR = 1.02, 95% CI = 0.90-1.15, I2 = 51%, P = 0.78; GG vs. CC, OR = 1.97, 95% CI = 1.04-3.74, I2 = 70%, P = 0.04; GC vs. CC, OR = 1.75, 95% CI = 1.12-2.75, I2 = 42%, P = 0.01; GG + GC vs. CC, OR = 1.85, 95% CI = 1.08-3.18, I2 = 63%, P = 0.03; and GG vs. GC + CC, OR = 1.28, 95% CI = 1.04-1.58, I2 = 39%, P = 0.02), and significance was also noted for IL-1RN VNTR under the dominant model (22 + 2L vs. LL, OR = 1.49, 95% CI = 1.01-2.19, I2 = 77%, P = 0.045) and allelic contrast model (2 vs. L, OR = 1.28, 95% CI = 1.00-1.64, I2 = 58.6%, P = 0.047). For IL-1β + 31C/T, significance was observed in the dominant model (CC + CT vs. TT, OR = 0.83, 95% CI = 0.69-0.99, I2 = 52%, P = 0.034) and the heterozygous model (CT vs. TT, OR = 0.80, 95% CI = 0.65-0.98, I2 = 60%, P = 0.04). For IL-1β + 511 C/T, a significant association was noted in four gene models (CT vs. TT, OR = 0.72, 95% CI = 0.63-0.83, I2 = 0%, P < 0.001; CC + CT vs. TT, OR = 0.74, 95% CI = 0.65-0.84, I2 = 0%, P < 0.001; CC vs. TT, OR = 0.77, 95% CI = 0.65-0.91, I2 = 30.9%, P = 0.003; C vs. T, OR = 0.87, 95% CI = 0.80-0.95, I2 = 38%, P = 0.001), but a significant relationship was not found in the recessive model (CC vs. CT + TT, OR = 1.09, 95% CI = 0.86-1.38, I2 = 57.1%, P = 0.25). In addition, borderline statistical significance was noted between IL-1β + 3954 Ins/Del and CRC in the homozygous model, but no significance was identified for IL-1β + 3737 G/A, Il-1β + 1464 G/C, and IL-1RN + 2018 T/C under all five genetic models. In the subgroup analysis of ethnic groups, significant associations with CRC were found for IL-1β + 31 (CC vs. TT: OR = 0.82, 95% CI = 0.67-0.99, I2 = 20.2%, P = 0.04; CT vs. TT: OR = 0.62, 95% CI = 0.47-0.82, I2 = 0%, P < 0.001; CC + CT vs. TT: OR = 0.69, 95% CI = 0.55-0.87, I2 = 29.7%, P = 0.001), IL-1β + 511 (CT vs. TT, OR = 0.65, 95% CI = 0.55-0.77, I2 = 0%, P < 0.001; CC + CT vs. TT, OR = 0.67, 95% CI = 0.58-0.78, I2 = 0%, P < 0.001; C vs. T, OR = 0.83, 95% CI = 0.75-0.92, I2 = 49.6%, P < 0.001) and IL-1RN + 2018 T/C in the allelic contrast model (T vs. C, OR = 0.66, 95% CI = 0.44-0.98, I2 = 0%, P = 0.04) among Asians but not in Caucasians. A significant association between IL-1β + 1464 G/C polymorphisms in Caucasians was observed under the recessive model (OR = 0.87, 95% CI = 0.77-0.98, I2 = 45%, P = 0.03). CONCLUSION The current meta-analysis demonstrated that IL-1α rs3783553, IL-1β + 31C/T, IL-1β + 511C/T, and IL-1RN VNTR are critical genes for CRC susceptibility.
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Affiliation(s)
- Li Liu
- Library, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Department of Epidemiology and Statistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Zhenglong Zhai
- Department of Hepatobiliary & Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Danyang Wang
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Yun Ding
- Library, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xiaoqing Chen
- Library, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qiqi Wang
- Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Zheyue Shu
- Department of Hepatobiliary & Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Minglan Wu
- Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Research Center for Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lei Chen
- Information Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xuelin He
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Dazhi Fan
- Foshan Institute of Fetal Medicine, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, 11 Renminxi Road, Foshan 528000, Guangdong, China; Department of Epidemiology and Statistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Faming Pan
- Department of Epidemiology and Statistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Meiyuan Xing
- Library, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Gong Y, Zhao W, Jia Q, Dai J, Chen N, Chen Y, Gu D, Huo X, Chen J. IKBKB rs2272736 is Associated with Gastric Cancer Survival. PHARMACOGENOMICS & PERSONALIZED MEDICINE 2020; 13:345-352. [PMID: 32884329 PMCID: PMC7443400 DOI: 10.2147/pgpm.s258761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 07/20/2020] [Indexed: 12/18/2022]
Abstract
Background IKBKB/IKKβ, as the core catalytic subunit of IκB kinase complex, participates in mediation of the classical NF-κB pathway, which has been linked to inflammation and tumorigenesis. Previous studies have shown that single nucleotide polymorphisms in IKBKB have been related to gastric cancer, but how they associate to the clinical outcome is not yet clear. In this study, we retrospectively investigated the associations between single nucleotide polymorphisms located in IKBKB and gastric cancer survival. Materials and Methods IKBKB rs2272736 was genotyped in 1210 patients with primary gastric cancer in a Han Chinese population, and the relationships between rs2272736 and overall survival were evaluated. We conducted Cox proportional hazards regression, which was performed to estimate the effects of single nucleotide polymorphisms on the overall survival of patients, adjusted for potential confounding variables. Results We found that patients with rs2272736 A allele in IKBKB had significantly prolonged overall survival time compared to those with the G allele (HR = 0.83, 95% CI = 0.68–1.00, P = 0.050). In addition, AA genotype was demonstrated to have reduced risk of death for gastric cancer compared with that associated with the GG/GA genotypes, which was more common in patients with cardiac carcinoma, well-differentiated and moderately differentiated tumors, TNM Ⅰ/Ⅱ stages and intestinal type. Conclusion Our findings have shown that single nucleotide polymorphism rs2272736 in IKBKB may be a promising prognostic biomarker which should promote personalized treatment.
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Affiliation(s)
- Yang Gong
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Wenjing Zhao
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Qiong Jia
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Jiali Dai
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Nan Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Yuetong Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Dongying Gu
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Xinying Huo
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Jinfei Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.,Cancer Center, Taikang Xianlin Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, People's Republic of China.,Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
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Najdaghi S, Razi S, Rezaei N. An overview of the role of interleukin-8 in colorectal cancer. Cytokine 2020; 135:155205. [PMID: 32721849 DOI: 10.1016/j.cyto.2020.155205] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 07/08/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023]
Abstract
Colorectal Cancer (CRC), a common malignancy, is developing globally among people. Mutagenic insults activate peripheral nucleated cells to secrete chemokines in order to cause an inflammatory state. Despite the presence of multi-retrieving factors, elevated production of minor cytokines may speed-up the sever stages of the baseline inflammation targeting normal compensatory mechanism. IL-8 is a pro-inflammatory cytokine that is believed to be up-regulated in CRC to proceed primary condition into tumor behavior via induction of proliferation, angiogenesis and metastasis. Here, we assess the role of IL-8 in every step of CRC from signaling pathway and formation to invasion and discuss around new perspective therapy that targets IL-8 to manage CRC worldwide incidence and survival rate, more precisely.
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Affiliation(s)
- Soroush Najdaghi
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sepideh Razi
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK.
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Ulhaq ZS, Garcia CP. Inflammation-related gene polymorphisms associated with Parkinson’s disease: an updated meta-analysis. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2020. [DOI: 10.1186/s43042-020-00056-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Abstract
Background
Strong evidence supports the involvement of inflammation processes in the development and progression of Parkinson’s disease (PD), where increasingly correlations have been identified between genetic variations in inflammation-related genes and PD. However, data varies between studies. Therefore, we conducted a meta-analysis to clarify associations between inflammation-related gene polymorphisms and PD risk.
Methods
All studies were identified through online databases. Pooled and stratified groups based on racial descent were assembled to evaluate associations between polymorphisms and PD.
Results
The pooled results showed that protective effects for PD were observed for (1) IL-1α -889 C/T in Asian populations (T vs. C, OR = 0.831, P = 0.031; TT + CT vs. CC, OR = 0.827, P = 0.049); (2) IL-6 -176 G/C in Caucasian populations (CC + GC vs. GG, OR = 0.656, P = 0.000; GC vs. GG, OR = 0.673, P = 0.000); (3) IL-8 -251 A/T (T vs. A, OR = 0.812, P = 0.041; TT vs. AT + AA, OR = 0.663, P = 0.012), particularly in Caucasian populations (TT vs. AT + AA, OR = 0.639, P = 0.010); (4) IL-10 -819 T/C (C vs. T, OR = 0.742, P = 0.034); (5) IL-18 -607 C/A (AA + CA vs. CC, OR = 0.597, P = 0.015; CA vs. CC, OR = 0.534, P = 0.005), and (6) CCR2 +190 G/A (AA vs. GA + GG, OR = 0.552, P = 0.018; AA vs. GG; OR = 0.554; 95% CI 0.336–0.914, P = 0.005). An increased risk of PD was associated with IL-10 -1082 G/A in Asian populations (A vs. G, OR = 1.731, P = 0.000; AA + GA vs. GG, OR = 1.910, P = 0.000). No significant associations with PD were observed for polymorphisms in IL-1β -511 C/T, IL-10 -592 C/A, IL-18 -137 G/C, TNFα -863 C/A, TNFα -857 C/T, TNFα -308 G/A, IFNΥ +874 T/A, and MCP1/CCL2 +2518 A/G.
Conclusions
We suggest that IL-1α -889, IL-6 -176, IL-8 -251, IL-10 -1082, IL-10 -819, IL-18 -607, and CCR2 +190 polymorphisms may be associated with PD risk; however, further studies must verify these conclusions.
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Ackermann A, Lafferton B, Plotz G, Zeuzem S, Brieger A. Expression and secretion of the pro‑inflammatory cytokine IL‑8 is increased in colorectal cancer cells following the knockdown of non‑erythroid spectrin αII. Int J Oncol 2020; 56:1551-1564. [PMID: 32236629 DOI: 10.3892/ijo.2020.5026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 02/25/2020] [Indexed: 11/05/2022] Open
Abstract
Non‑erythroid spectrin αII (SPTAN1) expression is decreased in ~40% of cases of MLH1‑deficient colorectal cancer (CRC). SPTAN1 knockdown reduces cell viability, cellular mobility and cell‑cell contact formation, indicating that the SPTAN1 plays an important role in tumour growth, attachment and in regulating the tumour microenvironment. Changes in the tumour microenvironment can affect the immune response. Therefore, in the present study, proteome arrays were used to analyse the expression of 119 different chemokines and soluble receptors in CRC cell lines in which mutL homologue 1 (MLH1) or SPTAN1 were knocked down. The levels of interleukin (IL)‑8 were significantly increased in the cells in which SPTAN1 was knocked down, both at the mRNA and protein level. ELISA demonstrated that the cells in which SPTAN1 was knocked down secreted increased quantities of IL‑8, and chemotaxis assays revealed the enhanced trafficking of neutrophils, which was induced by media containing higher levels of IL‑8. The IL‑8 receptors, CRCX1 and CRCX2, were expressed in all the cell lines examined; however, their expression was not directly associated with IL‑8 expression. The results of the present study thus demonstrated that CRC cells in which SPTAN1 was knocked down secreted significantly higher levels of IL‑8, which in‑turn increased the migration of neutrophilic granulocytes. As MLH1‑deficient CRC exhibits an increased infiltration of cytotoxic T‑cells and is associated with a decreased SPTAN1 expression, it can thus be hypothesized that CRC with a low SPTAN1 expression may release increased quantities of IL‑8, resulting in increased immune cell infiltration.
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Affiliation(s)
- Anne Ackermann
- Medical Clinic I, Biomedical Research Laboratory, University Clinic Frankfurt, D‑60590 Frankfurt am Main, Germany
| | - Barbara Lafferton
- Medical Clinic I, Biomedical Research Laboratory, University Clinic Frankfurt, D‑60590 Frankfurt am Main, Germany
| | - Guido Plotz
- Medical Clinic I, Biomedical Research Laboratory, University Clinic Frankfurt, D‑60590 Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Medical Clinic I, Biomedical Research Laboratory, University Clinic Frankfurt, D‑60590 Frankfurt am Main, Germany
| | - Angela Brieger
- Medical Clinic I, Biomedical Research Laboratory, University Clinic Frankfurt, D‑60590 Frankfurt am Main, Germany
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Huang Z, Zhou B, Li Z, Liu C, Zheng C, Zeng R, Hong C, Xu L, Li E, Peng Y, Xu Y. Serum interleukin-8 as a potential diagnostic biomarker in esophageal squamous cell carcinoma. Cancer Biomark 2020; 29:139-149. [PMID: 32623391 DOI: 10.3233/cbm-201687] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) has poor prognosis mainly due to the difficulty of making early diagnosis. Therefore, novel biomarkers are critically needed. OBJECTIVE We aimed to investigate the diagnostic value of serum interleukin-8 (IL-8) in ESCC. METHODS Data mining of TCGA was used to analyze expression level of IL-8 mRNA in esophageal carcinoma. Serum levels of IL-8 were measured in 103 ESCC patients and 86 normal controls by ELISA. Receiver operating characteristic (ROC) curve was used to evaluate its diagnostic accuracy. RESULTS IL-8 mRNA expression level and serum IL-8 concentration were both statistically higher in patients than normal controls (P< 0.001). ROC curve demonstrated that the optimum diagnostic cut-off for serum IL-8 was 80.082 pg/mL, providing an area under the curve (AUC) of 0.694 (95% CI: 0.620-0.768), with specificity of 86.0% and sensitivity of 42.7%. The AUC for early-stage ESCC was 0.618 (95% CI: 0.499-0.737), with sensitivity of 35.3% and specificity of 86.0%. Kaplan-Meier analysis and the log-rank test indicated that IL-8 may not be a prognostic predictor for ESCC. CONCLUSIONS Serum IL-8 was highly expressed in ESCC patients and may be a potential marker for early diagnosis of ESCC.
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Affiliation(s)
- Zeting Huang
- Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Bin Zhou
- Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Zheng Li
- Shantou University Medical College, Shantou, Guangdong, China
- Shantou University Medical College, Shantou, Guangdong, China
| | - Cantong Liu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou, Guangdong, China
| | - Chunwen Zheng
- Shantou University Medical College, Shantou, Guangdong, China
| | - Ruijie Zeng
- Shantou University Medical College, Shantou, Guangdong, China
| | - Chaoqun Hong
- Department of Oncological Laboratory Research, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Liyan Xu
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, China
| | - Enmin Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, China
| | - Yuhui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou, Guangdong, China
| | - Yiwei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou, Guangdong, China
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Association of polymorphisms in IL-8, MMP-1 and MMP-13 with the risk and prognosis of oral and oropharyngeal squamous cell carcinoma. Arch Oral Biol 2019; 108:104547. [PMID: 31525531 DOI: 10.1016/j.archoralbio.2019.104547] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/02/2019] [Accepted: 08/28/2019] [Indexed: 12/28/2022]
Abstract
OBJECTIVE This study investigated the risk and prognostic value of single nucleotide polymorphisms (SNP) inIL-8, MMP-1 and MMP-13 in oral and oropharyngeal squamous cell carcinomas (SCCs). DESIGN SNPs rs2227532 and rs4073 inIL-8, rs2071230 and rs470558 in MMP-1, and rs2252070 in MMP-13 were genotyped in 125 oral and oropharyngeal SCC patients and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as SNP-SNP interaction and gene-environmental factor (GxE) interaction. Univariate and multivariate methods were applied for survival analyses. RESULTS With exception of rs2227532, all the SNPs were in Hardy-Weinberg equilibrium in the control. No associations between rs4073 in IL-8 and rs2071230 and rs470558 in MMP-1 were observed, but rs2252070 in MMP-13, in the dominant model, was associated in a protective manner to oral and oropharyngeal SCC (OR: 0.20, 95% CI: 0.06-0.71, p = 0.007). All SNPs interact significantly with cigarette smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC, but they showed no influence on survival of the patients. CONCLUSIONS Our results show that rs2252070 inMMP-13 may confer protection effect against oral and oropharyngeal SCC. In addition, the combined effects of IL-8 (rs4073), MMP-1 (rs2071230 and rs470558) and MMP-13 (rs2252070) with environmental carcinogens, such as tobacco and alcohol, are related to increased risk for oral and oropharyngeal SCC development.
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Huang C, Wang L, Song H, Wu C. Interactive effects of AURKA polymorphisms with smoking on the susceptibility of oral cancer. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:2333-2337. [PMID: 31174434 DOI: 10.1080/21691401.2019.1601101] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Chao Huang
- Department of Stomatology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Lili Wang
- Department of Prosthodontics, Tianjin Stomatological Hospital, Tianjin, China
| | - Hongguang Song
- Department of Stomatology, Beijing DCN Orthopaedic Hospital, Beijing, China
| | - Cungang Wu
- Department of Ultrasonography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
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