Stepwise Expression of CDKN2A and RB1 Proteins in Esophageal Mucosa From Patients at High Risk for Squamous Cell Carcinoma

Müller, L.; Meurer, Luíse; Lopes, Antônio B.; Antunes, Luciana da Conceição; Vanazzi, Sara S.; Fagundes, Renato Borges

doi:10.1097/pai.0000000000000011

Cited by 5 publications

(5 citation statements)

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“…TP53 Pro72 allele increases the risk of ESCC. In previous research, CDKN2A/RB1 was not expressed in the esophageal mucosa of patients without risk factors whereas p16/pRb expression increased in patients exposed to risk factors or with ESCC (7,8). Although numerous single genetic studies and genetic pathway studies have provided many important insights of the development and prognosis of ESCC, they have not provided clues from the perspective of systems biology.…”

Section: Introductionmentioning

confidence: 94%

Network and pathway-based analysis of genes associated with esophageal squamous cell carcinoma

He¹,

Yuan²,

He³

et al. 2023

Ann Transl Med

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Background Although diagnostic methods and treatments have improved over the last few years, the 5-year survival rate of esophageal squamous cell carcinoma (ESCC) patients remains generally poor. The development of high-throughput technology has facilitated great achievements in localization of ESCC-related genes. To take a further step toward a thorough understanding of ESCC at a molecular level, the potential pathogenesis of ESCC needs to be deciphered. Methods The interaction of ESCC-related genes was explored by collecting genes associated with ESCC and then performing gene enrichment assays, pathway enrichment assays, pathway crosstalk analysis, and extraction of ESCC-specific subnetwork to describe the relevant biochemical processes. Results Through Gene Ontology (GO) enrichment analysis, many molecular functions related to response to chemical, cellular response to stimulus, and cell proliferation were found to be significantly enriched in ESCC-related genes. The results of pathway and pathway crosstalk analysis showed that pathways associated with multiple malignant tumors, the immune system, and metabolic processes were significantly enriched in ESCC-related genes. Through the analysis of specific subnetworks, we obtained some novel ESCC-related potential genes, such as MUC13 , GSTO1 , FIN , GRB2 , CDC25C , and others. Conclusions The molecular mechanism of ESCC is extremely complex. Some inducing factors change the expression status of many genes. The abnormal expression of genes mediates the biological processes involved in immunity and metabolism, apoptosis, and cell proliferation, leading to the occurrence of tumors. The genes MUC13 , RYK , and FIN may be potential prognostic indicators of ESCC; GRB2 and CDC25C may be potential targets of ESCC in proliferation. Our work may provide valuable information for further understanding the molecular mechanisms for the development of ESCC.

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Section: Introductionmentioning

confidence: 94%

Network and pathway-based analysis of genes associated with esophageal squamous cell carcinoma

He¹,

Yuan²,

He³

et al. 2023

Ann Transl Med

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“…The molecular progression from dysplasia to invasive OSCC has not been well studied, however dysregulation of TP53 and cell cycle regulators are prominent characteristics of OSCC, which may also be detected in precursor lesions 31. Abnormal P53 protein accumulation has been demonstrated in oesophagitis adjacent to dysplasia and carcinoma and increased expression of CDKN2A/RB1 has been associated with stepwise progression from inflammation to cancer in oesophageal lesions 32,33. Differentiation between normal and dysplastic tissue for accurate risk stratification is challenging, however evaluation of genes differentially expressed in normal oesophageal mucosa and OSCC has identified two candidate biomarkers; TNFAIP3 and CHN , levels of which increase through the normal tissue-dysplasia-carcinoma sequence, implying these could aid in future diagnosis of dysplasia or invasive OSCC 34…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Oesophageal cancer

Smyth

Lagergren

Fitzgerald

et al. 2017

Nat Rev Dis Primers

761

641

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Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries. Preneoplastic lesions are identifiable for both OSCC and OAC; these are frequently amenable to endoscopic ablative therapies. Most patients with oesophageal cancer require extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical resection. Patients with advanced or metastatic oesophageal cancer are treated with palliative chemotherapy; those who are human epidermal growth factor receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno-oncology therapies have also shown promising early results in OSCC and OAC. In this Primer, we review state-of-the-art knowledge on the biology and treatment of oesophageal cancer, including screening, endoscopic ablative therapies and emerging molecular targets, and we discuss best practices in chemotherapy, chemoradiotherapy, surgery and the maintenance of patient quality of life.

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“…However, one other work directed the researchers a linear relationship between up regulation of CDKN2A protein and the severity of histological transformation of mucosa ultimately causes malignant transformation. That was the controversial among many studies [24]. Yang et al [25] demonstrated in his study that the survival status depends on P 16 expression status in the patients with non-oropharyngeal head & neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 98%

Decreased Expression of P16 Indicates the Postoperative Poor Prognosis of Esophageal Squamous Cell Carcinoma Patients

Cheng¹

2019

NACS

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Globally esophageal cancer effect 480,000 new cases as well as 400,000 deaths per year, which is the 6 th leading reason cancer death and suppose as 8 th most common cancer [1]. Between two main histological types (esophageal squamous cell carcinoma and esophageal adenocarcinoma), though esophageal adenocarcinoma (EAC) high incidence in western countries, yet esophageal squamous cell carcinoma (ESCC) is worst histological type of the cancer. Lack of or ignorance of early symptoms and high invasive characteristics of ESCC responsible for poor outcome. But now-a-days new and advance clinical treatment favor on increase 5-year overall survival almost 42% [2]. Consequently, to determine prognostic outcome, etiology of progression of disease & determine treatment protocol; one of the best ways is prediction of prognostic indicators. CDKN2A (P 16 ) is one of the significant biomarkers that regulates cell cycle as tumor suppressor gene. Locus of this protein is genetically more susceptible in many cancers [3]. Hence, P 16 pondered as analyst of biological characteristics of many malignancies, for instance gastric carcinoma, cervical carcinoma, endometrial carcinoma, lung cancer, breast cancer, anal cancer, colorectal cancer, nasopharyngeal cancer, and so on [4,5]. Usually, P 16 upregulated in normal cells and maintain normal cell cycle, but cancerous cell its down regulated and loss its power to control normal cell cycle. Though many researches held to observe the prognostic role of this protein regulation in ESCC in last decades, yet the accurate decisions are uncertain [6]. The aim of our study is to determine the prognostic value of P 16 and effect of its expression status on patient's survival and disease progression [7].

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Stepwise Expression of CDKN2A and RB1 Proteins in Esophageal Mucosa From Patients at High Risk for Squamous Cell Carcinoma

Cited by 5 publications

References 35 publications

Network and pathway-based analysis of genes associated with esophageal squamous cell carcinoma

Network and pathway-based analysis of genes associated with esophageal squamous cell carcinoma

Oesophageal cancer

Decreased Expression of P16 Indicates the Postoperative Poor Prognosis of Esophageal Squamous Cell Carcinoma Patients

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