Inflammatory profile in cervical cancer: influence of purinergic signaling and possible therapeutic targets

Franciosi, Maria Luiza Mukai; Carmo, Thiago Inácio Teixeira do; Zanini, Daniela; Cardoso, Andréia Machado

doi:10.1007/s00011-022-01560-8

Cited by 7 publications

(6 citation statements)

References 57 publications

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“…The KEGG analysis showed that the IL-17 signaling pathway has a significant change in CC vs. CK and HSIL vs. CK groups ( Supplementary Materials Figures S7 and S8 ), which is consistent with most reports that the IL-17 pathway plays important roles in cervical cancer and HSIL [ 21 , 22 , 23 ]. The viral protein interaction with cytokine and cytokine receptor pathway also has an outstanding performance in CC vs. CK and CC vs. HSIL groups ( Supplementary Figure S7 and S8 ), which is consistent with the fact that the etiology of cervical cancer is associated with persistent high-risk HPV infection.…”

Section: Discussionsupporting

confidence: 89%

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion

Han

Zhang

Sun

et al. 2022

JCM

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Objective: The process of normal cervix changing into high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer is long and the mechanisms are still not completely clear. This study aimed to reveal the protein profiles related to HSIL and cervical cancer and find the diagnostic and prognostic molecular changes. Methods: Data-independent acquisition (DIA) analysis was performed to identify 20 healthy female volunteers, 20 HSIL and 20 cervical patients in a cohort to screen differentially expressed proteins (DEPs) for the HSIL and cervical cancer. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional annotation of DEPs; the protein–protein interaction (PPI) and weighted gene co-expression network analysis (WGCNA) were performed for detection of key molecular modules and hub proteins. They were validated using the Enzyme-Linked Immunosorbent Assay (ELISA). Results: A total of 243 DEPs were identified in the study groups. GO and KEGG analysis showed that DEPs were mainly enriched in the complement and coagulation pathway, cholesterol metabolism pathway, the IL-17 signaling pathway as well as the viral protein interaction with cytokine and cytokine receptor pathway. Subsequently, the WGCNA analysis showed that the green module was highly correlated with the cervical cancer stage. Additionally, six interesting core DEPs were verified by ELISA, APOF and ORM1, showing nearly the same expression pattern with DIA. The area under the curve (AUC) of 0.978 was obtained by using ORM1 combined with APOF to predict CK and HSIL+CC, and in the diagnosis of HSIL and CC, the AUC can reach to 0.982. The high expression of ORM1 is related to lymph node metastasis and the clinical stage of cervical cancer patients as well as the poor prognosis. Conclusion: DIA-ELSIA combined analysis screened and validated two previously unexplored but potentially useful biomarkers for early diagnosis of HSIL and cervical cancer, as well as possible new pathogenic pathways and therapeutic targets.

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Section: Discussionsupporting

confidence: 89%

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion

Han

Zhang

Sun

et al. 2022

JCM

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“…Furthermore, cytokines released during chronic inflammation can induce angiogenesis, alter the expression of oncogenes and tumor suppressor genes, and inhibit apoptosis, resulting in abnormal inflammatory signalling pathways; chronic inflammation also promotes the establishment of an immunosuppressive tumor microenvironment (TME) ( Santella et al, 2022 ; Yang et al, 2021 ). Although both immunity and inflammation are fundamental characteristics of the TME, the activation of systemic immune responses by malignant tumors allows the detection of inflammatory cells surrounding tumor cells, suggesting that blood inflammatory cells can serve as biomarkers for the diagnosis of malignant tumors ( Franciosi et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study

Wang,

Dong

2024

PeerJ

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Objective The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson’s correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

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“…[ 6 , 7 ] The binding and regulation of these 2 proteins by p53 and pRb, 2 major intracellular tumor suppressor proteins, can significantly alter the cell growth cycle, DNA repair, and activation of the cyclooxygenase-2 inflammatory pathway, resulting in increased inflammation and tumorigenesis. [ 8 , 9 ] Therefore, inflammation plays a crucial role in the tumorigenesis of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have confirmed that the tumor microenvironment of cervical cancer is associated with the production of several cytokines, including pro-inflammatory cyclooxygenase-2, tumor necrosis factor-alpha, interleukin 1 (IL-1), IL-6, IL-17, IL-18, hypoxia-inducible factor-1, reactive oxygen species, and anti-inflammatory factors IL-10 and transforming growth factor beta; thus, changes in these components can be observed throughout the pathological process. [ 8 , 10 ] Tumor necrosis factor-alpha triggers other inflammatory mediators that participate in inflammatory responses and promote tumorigenesis. In cervical cells, it induces bidirectional regulatory proteins that, together with IL-1α, stimulate the proliferation of permanent cervical cells.…”

Section: Introductionmentioning

confidence: 99%

“…[ 15 ] purinergic ligand-gated ion channel 7 and adenosine A(2A) receptors are considered novel therapeutic targets because blocking purinergic ligand-gated ion channel 7 results in reduced release of proinflammatory cytokines, whereas blocking adenosine A(2A) increases the activation of cytotoxic T lymphocytes to fight cervical cancer. [ 8 ] Increasing dietary intake of natural anti-inflammatory compounds such as curcumin and resveratrol helps prevent the development of cancer. [ 16 , 17 ] Anti-inflammatory drugs typically target oncogenic viruses to generate signaling pathways for persistent infection, thereby countering the role of persistent infection in cancer progression.…”

Section: Introductionmentioning

confidence: 99%

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A bibliometric analysis of global research trends of inflammation in cervical cancer: A review

Kang,

Qiu,

Wei

et al. 2023

Medicine

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Cervical cancer is a common malignant tumor and a leading cause of death in women worldwide. It plays a crucial role in tumorigenesis and progression of cervical cancer. A total of 1606 references on inflammation in cervical cancer were retrieved from the Web of Science Core Collection and visual analysis was performed using VOSviewer. Inflammation in cervical cancer has attracted the attention of researchers. Even though China is the country that publishes the most papers, with the most of the top-ranking institutions, there is no extensive collaboration and exchange of papers by Chinese scholars. PLOS One is a popular journal on inflammation in cervical cancer. Instead, authors from other countries perform better, for example, the Sjoerd H. Van Der Burg is the most widely cited author and “M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4 + Th1 cells” (Moniek Heusinkveld, Leiden University Medical Center) is the most cited article of inflammation in cervical cancer. Keywords associated with “apoptosis,” “HPV,” “NF-κB,” and “oxidative stress have been used in many studies, and keywords associated with “apoptosis,” “human papillomavirus (HPV),” “NF-κB,” and “oxidative stress” are involved in many studies, and there may be more research ideas in the future. From the perspective of precision medicine, more substantive research articles can promote scientific value, strengthen communication and cooperation, produce more extensive research results, and greatly promote the clinical diagnosis and treatment of cervical cancer. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Inflammatory profile in cervical cancer: influence of purinergic signaling and possible therapeutic targets

Cited by 7 publications

References 57 publications

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion

Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study

A bibliometric analysis of global research trends of inflammation in cervical cancer: A review

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