Analysis of systemic inflammatory response in the carcinogenic process of uterine cervical neoplasia

Lages, Elisa Lopes e; Belo, Andrezza V.; Andrade, Sílvia Passos; Rocha, Monaliza Angela; Freitas, Gustavo Ferreira de; Lamaita, Rívia Mara; Traiman, Paulo; Silva-Filho, Agnaldo L.

doi:10.1016/j.biopha.2011.06.010

Cited by 19 publications

(11 citation statements)

References 28 publications

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“…Levels of IFNG were lower in the group of women with CC compared to controls. This is in accordance with previous works indicating a shift towards a T helper 2-type (Th2) cytokine pattern in CC [ 56 ] and that increased serum levels of IL-6, IL-10, and TGFB1 are associated with progression of CC during different stages, all of which have the potential to be angiogenic amplifiers [ 57 ].…”

Section: Discussionsupporting

confidence: 93%

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Torres-Poveda¹,

Burguete-García²,

Bahena-Román³

et al. 2016

BMC Cancer

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BackgroundAlterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age.MethodsPeripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA.ResultsAfter analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP (−590C > T IL-4), C of SNP (−573G > C IL-6), A of SNP (−592C > A IL-10), T of SNP (−819C > T IL-10) and T of SNP (−509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475–2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208–2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332–2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192–2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354–2.701, p = 0.0001), respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases.ConclusionThe significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of susceptibility to this disease.

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Section: Discussionsupporting

confidence: 93%

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Torres-Poveda¹,

Burguete-García²,

Bahena-Román³

et al. 2016

BMC Cancer

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“…23 The SIR is widely participated in the initiation and progression of solid tumors including cervical cancer, such as malignant proliferation, survival, invasion, angiogenesis, and metastasis. [24][25][26][27] Previous studies have reignited the interest of cancer researchers in the concept of a correlation between SIR and tumor outcomes. 9,10,28,29 Accordingly, previous researches have undertaken in-depth studies involving SIRbased predictive indicators such as CRP, 30 platelet-tolymphocyte ratio, 31 neutrophil-to-lymphocyte ratio, 31,32 and modified Glasgow prognostic score (mGPS) 33,34 in the outcomes of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Values of Systemic Inflammation Response (SIR) Parameters in Resectable Cervical Cancer

et al. 2019

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Background: Cervical carcinoma is the leading cause of cancer mortality in women. C-reactive protein (CRP), albumin (ALB), globulin (GLB), lactate dehydrogenase (LDH), and albumin-to-globulin ratio (AGR) are indicators of systemic inflammation response correlated with tumor outcomes. Methods: This study recruited 110 patients with cervical cancer. The patients were divided into 2 groups according to pretreatment median values of CRP, ALB, GLB, LDH, and AGR. The post/preradiotherapy or post/pretreatment ratios were defined as rates of pretreatment CRP, ALB, GLB, LDH, and AGR values and the corresponding ones obtained after radiotherapy or whole treatment. Results: Higher pretreatment CRP or LDH levels were correlated with worse progression-free survival (PFS) and overall survival (OS). Increased post/preradiotherapy CRP ratio was correlated with worse PFS and OS, increased post/preradiotherapy LDH ratio was correlated with worse PFS. Increased post/pretreatment CRP ratio was correlated with worse PFS and OS, not-increased post/pretreatment AGR ratio was correlated with worse OS. Cox regression analysis model indicated that, moderately or poorly of differentiation, higher pretreatment CRP or LDH levels were independently associated with worse PFS, higher pretreatment CRP or LDH levels and increased post/pretreatment CRP ratio were independently associated with worse OS. Conclusion: CRP, LDH, or AGR are correlated with outcomes of resectable cervical cancer.

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“…Compared to Methylation-M and Methylation-L, Methylation-H exhibited a significantly improved OS. The hallmarks of tumors, including KRAS signaling, TNFa signaling via NF-jB, inflammatory response, epithelial-mesenchymal transition, and interferongamma response, were enriched in Methylation-M and Methylation-L. A great deal of research work has suggested that these biological processes or pathways play a significant role in tumorigenesis and the progression of CC (Kang et al, 2007;Kloth et al, 2005;Lages et al, 2011;Lee et al, 2008). We reasoned that the HPV-related methylation signature might take an important part in CC via the above biological processes or pathways.…”

Section: Subtype Identificationmentioning

confidence: 99%

HPV‐related methylation‐based reclassification and risk stratification of cervical cancer

Yang

Wang

et al. 2020

Molecular Oncology

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Human papillomavirus (HPV) is a clear etiology of cervical cancer (CC). However, the associations between HPV infection and DNA methylation have not been thoroughly investigated. Additionally, it remains unknown whether HPV‐related methylation signatures can identify subtypes of CC and stratify the prognosis of CC patients. DNA methylation profiles were obtained from The Cancer Genome Atlas to identify HPV‐related methylation sites. Unsupervised clustering analysis of HPV‐related methylation sites was performed to determine the different CC subtypes. CC patients were categorized into cluster 1 (Methylation‐H), cluster 2 (Methylation‐M), and cluster 3 (Methylation‐L). Compared to Methylation‐M and Methylation‐L, Methylation‐H exhibited a significantly improved overall survival (OS). Gene set enrichment analysis (GSEA) was conducted to investigate the functions that correlated with different CC subtypes. GSEA indicated that the hallmarks of tumors, including KRAS signaling, TNFα signaling via NF‐κB, inflammatory response, epithelial–mesenchymal transition, and interferon‐gamma response, were enriched in Methylation‐M and Methylation‐L. Based on mutation and copy number variation analyses, we found that aberrant mutations, amplifications, and deletions among the MYC, Notch, PI3K‐AKT, and RTK‐RAS pathways were most frequently detected in Methylation‐H. Additionally, mutations, amplifications, and deletions within the Hippo, PI3K‐AKT, and TGF‐β pathways were presented in Methylation‐M. Genes within the cell cycle, Notch, and Hippo pathways possessed aberrant mutations, amplifications, and deletions in Methylation‐L. Moreover, the analysis of tumor microenvironments revealed that Methylation‐H was characterized by a relatively low degree of immune cell infiltration. Finally, a prognostic signature based on six HPV‐related methylation sites was developed and validated. Our study revealed that CC patients could be classified into three heterogeneous clusters based on HPV‐related methylation signatures. Additionally, we derived a prognostic signature using six HPV‐related methylation sites that stratified the OS of patients with CC into high‐ and low‐risk groups.

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Analysis of systemic inflammatory response in the carcinogenic process of uterine cervical neoplasia

Cited by 19 publications

References 28 publications

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

Prognostic Values of Systemic Inflammation Response (SIR) Parameters in Resectable Cervical Cancer

HPV‐related methylation‐based reclassification and risk stratification of cervical cancer

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