MMP13 and SERPINB2 As Novel Biomarkers For Hypopharyngeal Cancer
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Austin Journal of Clinical Pathology
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MMP13 and SERPINB2 as Novel Biomarkers for Hypopharyngeal Cancer Lv F1, Huang W 2 and Ji X 3* 1 Department of Oncology, Shengjing Hospital of China Medical University, China 2 Department of Pathology, Shengjing Hospital of China Medical University, People’s Republic of China 3 Department of Otorhinolaryngology Head and Neck Surgery, the First Hospital of China Medical University, People’s Republic of China *Corresponding author: Xu author: Xu Ji, Department of Otorhinolaryngology Head and Neck Surgery, the First Hospital of China Medical University, Shenyang 110001, Liaoning, People’s Republic of China Received: September 21, 2020; Accepted: Received: September 2020; Accepted: October October 13, 2020; Published: Published: October October 20, 2020
Ab st rac t
Matrix Metalloproteinase Metalloproteinase (MMP)13 and serine peptidase inhibitor, clade B, member 2 (SERPINB2) are important components of the extracellular matrix and play a regulatory role in tumor stromal remodeling. The purpose of the study is to evaluate the expression of MMP13 and SERPINB2 in hypopharyngeal cancer. We utilized the public datasets to nd the differentially expressed genes of hypopharyngeal cancer, which were veried by immunohistochemistry immunohistochemistry.. At the same time, the role of differential expressed genes in prognosis was explored. We found that MMP13 is upregulated and SERPINB2 is downregulated in public datasets. We conrmed this conclusion by immunohistochemistry of hypopharyngeal cancer tissues and found that MMP13 and SERPINB2 were related to some clinicopathological factors. Moreover, SERPINB2 is an independent prognostic factor for hypopharyngeal cancer patients. MMP13 and SERPINB2 may predict the early recurrence of hypopharyngeal cancer. cancer. MMP13 combined with SERPINB2 may be potential prognostic biomarkers and drug targets in hypopharyngeal cancer. Keywords: Hypopharyngeal neoplasms; Matrix metalloproteinase 13;
Plasminogen activator inhibitor 2; Immunohistochemistry
Abbreviations Abbreviation s AUC: Area Under ROC Curve; CI: Confidence Interval; DAB: 3, 3’-Diaminobenzidine tetrahydrochloride; DEGs: Differentially Expressed Genes; ECM: Extracellular Matrix; FC: Fold-Change; GEO: Gene Expression Omnibus; H& H&E: Hematoxylin and Eosin; H3K4me3: Histone H3 trimethylation at lysine 4; HR: Hazard Ratio; ING: Inhibitor o Growth; MMPs: Matrix Metalloproteinases; PAI: Plasminogen Activator Inhibitor; CGA: Te Cancer Genome Atlas; uPA: urokinase type Plasminogen Activator; WHO: World Health Organization
Introduction As an uncommon malignant tumor, hypopharyngeal cancer
wide range o proteolytic unctions, and MMP13 participates in various physiological and pathological processes [3]. SERPINB2, also known as PAI-2, is a member o the SERPIN superamily o serine protease inhibitors. SERPINB2 mainly inhibits uPA and tissue plasminogen activator [4]. Previous studies have shown that MMP13 [5,6] or SERPINB2 [7,8] are associated with the occurrence or prognosis o different tumors. However, until now, there has been no report on the expression and regulation o MMP13 and SERPINB2 in hypopharyngeal cancer. As a rare tumor, hypopharyngeal cancer also lacks markers or diagnosis and prognosis. Tis is the first study to investigate the expression and correlation o MMP13 and SERPINB2 in hypopharyngeal carcinoma. Trough public datasets and immunohistochemistry, we showed the
accounts or 3–5% o head and neck tumors [1]. Most pathological types o hypopharyngeal cancer are squamous cell carcinoma. Due to the occult anatomical location o hypopharyngeal cancer and poor surgical effect, local recurrence or distant metastasis ofen occurs in patients with hypopharyngeal cancer ollowing surgery. Pharyngeal fistula also affects the quality o lie o hypopharyngeal cancer patients. Tereore, it is necessary to search orhypopharyngeal cancer markers.
expression changes and correlations MMP13 and in hypopharyngeal cancer. MMP13 andoSERPINB2 are SERPINB2 related to the survival o hypopharyngeal carcinoma patients and may predict early recurrence. Tese findings suggest that MMP13 and SERPINB2 play an important role in hypopharyngeal cancer and may be a potential prognostic marker and therapeutic targets or patients with hypopharyngeal cancer.
umor stroma is mainly composed o collagen fibers, vascular vessels, and Extracellular Matrix (ECM) components. ECM components are over-deposited in tumor tissues and unction in nourishing tumor cells. Te system composed o urokinase type Plasminogen Activator (uPA), plasmin, Plasminogen Activator Inhibitor (PAI), and Matrix Metalloproteinases (MMPs) is one o the main ways to regulate ECM degradation. MMP13, also known as Collagenase 3, can degrade a variety o ECM components, including
Public datase datasets ts sea searching rching
tenascin C, fibronectin, and type I–IV collagen [2]. MMP13 has a
the Organism and Expression profiling by array in the ype.
Austin J Clin Pathol - Volume 7 Issue 2 - 2020 ISSN : 2381-9170 | www.austinpublishinggroup.com Ji et al. © All rights are reserved
Methods From the National Center o Biotechnology Inormation Gene Expression Omnibus (GEO) database (https://www.ncbi. nlm.nih.gov/gds/), we searched raw gene expression data o the hypopharyngeal cancer as the ollowing oll owing key terms: (hypopharyngeal or hypopharynx) and (cancer or tumor or carcinoma or neoplasm). Te publication time was not limited. Homo sapiens was selected in
Citation: Lv Lv F, Huang W and Ji X. MMP13 and SERPINB2 as Novel Biomarkers for Hypopharyngeal Cancer. Citation:
Austin J Clin Pathol. 2020; 7(2): 1065.
Ji X
Austin Publishing Group
GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) is an online tool provided by GEO, which is based on the R language limma package [9]. GEO2R was used to screen DEGs (differentially expressed genes) between hypopharyngeal cancer and non-cancerous samples in the GEO datasets and we urther visualized DEGs by volcano plot [10]. A P-value
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