Epigenetic Regulation: A Link between Inflammation and Carcinogenesis

Vezzani, Bianca; Carinci, Marianna; Previati, Maurizio; Giacovazzi, Stefania; Sala, Mario Della; Gafà, Roberta; Lanza, Giovanni; Wieckowski, Mariusz R.; Pinton, Paolo; Giorgi, Carlotta

doi:10.3390/cancers14051221

Cited by 21 publications

(11 citation statements)

References 159 publications

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“…Using this proposed tool, in-clinic risk-stratification of ccRCC could be improved in terms of both accuracy and convenience. In addition, as tumorigenesis and development of solid carcinomas in humans are facilitated by a strong proinflammatory environment (50)(51)(52), it is hypothesized that the IPS score, which was constructed using IGs, can perform well when applied for the prognosis estimation of other tumor types, such as neuroblastoma or osteosarcoma. The immune microenvironment serves a significant role in tumor development (17), particularly in ccRCC (53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma

et al. 2022

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Clear cell renal cell carcinoma (ccRCC) are typically situated in a complex inflammatory and immune microenvironment, which has been reported to contribute to the unfavorable prognosis of patients with ccRCC. There would be beneficial clinical implications for elucidating the roles of its molecular characteristics in the inflammatory microenvironment. This is because it would facilitate the development of reliable biomarkers for pre-stratification prior to the designation of individualized treatment strategies. In the present study, RNA-sequencing data from 607 patients were retrospectively analyzed to elucidate the profile of inflammatory molecules. Based on this, an inflammatory prognostic signature (IPS) was developed and further validated using clinical ccRCC samples. Subsequently, the associated mechanisms in terms of the immune microenvironment and molecular pathways were then investigated. This proposed IPS was found to exhibit superior accuracy compared with the criterion of a good prognostic model for the prediction of patient prognosis from ccRCC [area under the receiver operating characteristic curve (AUC)=0.811] in addition to being an independent factor for prognostic risk stratification [hazard ratio: 11.73 (95% CI, 26.98-5.10); log-rank test, P<0.001]. Pathologically, ccRCC cells identified as high-risk according to their IPS presented with a more malignant tumor structure, including voluminous eosinophilic cytoplasm, acinar/lamellar/tubular growth patterns and atypic nuclei. High-risk ccRCC also exhibited higher infiltration levels by four types of immune cells, including T regulatory cells, but lower infiltration levels by mast cells. Pathways associated with immune-inflammation interaction, including the IL-17 pathway, were found to be upregulated in IPS-identified high-risk ccRCC. Furthermore, by combining the IPS with clinical factors, an integrated prognostic index was developed and validated for increasing the accuracy of patient risk-stratification for ccRCC (AUC= 0.911). In conclusion, the complex regulatory mechanisms and molecular characteristics involved in ccRCC-inflammation interaction, coupled with their prognostic potential, were systematically elucidated in the present study. This may have important implications in furthering the understanding into the molecular mechanisms underlying this ccRCC-inflammation interaction, which can in turn be exploited for identifying high-risk patients with ccRCC prior to designing their clinical treatment strategy.

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Section: Discussionmentioning

confidence: 99%

A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma

et al. 2022

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“…In turn, ncRNAs can modify the epigenome by interacting with epigenetic regulators or modifying their expression, thereby establishing a complex network that is perturbed during carcinogenesis. This complex network could be altered in response to environmental changes and/or stress responses, including exposure to toxic pollutants or carcinogenic agents [ 104 , 105 ]. Emerging studies are starting to link distinct types of mutations in ncRNA genes with cancers.…”

Section: Noncoding Rnas In Ovarian Cancermentioning

confidence: 99%

Extracellular Vesicles-ceRNAs as Ovarian Cancer Biomarkers: Looking into circRNA-miRNA-mRNA Code

Cammarata

Barraco

Giusti

et al. 2022

Cancers

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Ovarian cancer (OC) is one of the most lethal gynecologic malignancies in females worldwide. OC is frequently diagnosed at an advanced stage due to a lack of specific symptoms and effective screening tests, resulting in a poor prognosis for patients. Age, genetic alterations, and family history are the major risk factors for OC pathogenesis. Understanding the molecular mechanisms underlying OC progression, identifying new biomarkers for early detection, and discovering potential targets for new drugs are urgent needs. Liquid biopsy (LB), used for cancer detection and management, consists of a minimally invasive approach and practical alternative source to investigate tumor alterations by testing extracellular vesicles (EVs), circulating tumor cells, tumor-educated platelets, and cell-free nucleic acids. EVs are nanosize vesicles shuttling proteins, lipids, and nucleic acids, such as DNA, RNA, and non-coding RNAs (ncRNAs), that can induce phenotypic reprogramming of target cells. EVs are natural intercellular shuttles for ncRNAs, such as microRNAs (miRNAs) and circular-RNAs (circRNAs), known to have regulatory effects in OC. Here we focus on the involvement of circRNAs and miRNAs in OC cancer progression. The circRNA-microRNA-mRNA axis has been investigated with Circbank and miRwalk analysis, unraveling the intricate and detailed regulatory network created by EVs, ncRNAs, and mRNAs in OC.

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“…Recently accumulating evidence indicates that chronic inflammation plays an important role in the progression of cancer, via inflammation-mediated epigenetic alterations of cancer cells [ 27 29 ]. In ovarian cancer, epigenetic modification of histone such as suppression of H2B ubiquitylation has been shown to induce the upregulation of TNF-α and IL-6 along with increased migration of HGSC cells [ 30 ].…”

Section: Pathology and Epigenetics In Peritoneal Dissemination Of Hgscmentioning

confidence: 99%

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

et al. 2022

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Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.

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Epigenetic Regulation: A Link between Inflammation and Carcinogenesis

Cited by 21 publications

References 159 publications

A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma

A novel inflammation‑associated prognostic signature for clear cell renal cell carcinoma

Extracellular Vesicles-ceRNAs as Ovarian Cancer Biomarkers: Looking into circRNA-miRNA-mRNA Code

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

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