| Objective：Laryngeal carcinoma is a very common malignant tumor inhead and neck, around93%-99%of which is laryngeal squamous cellcarcinoma. There are two most common laryngeal cancers–supraglotticcarcinoma and glottic carcinoma: the former has poorer prognosis andexpresses higher incidence of cervical lymph node metastasis. The occurrence,development and metastasis of laryngeal cancer are a multi-stage processinvolving multiple genes and factors, and the study of supraglottic carcinomawill make remarkable contributions to effective prevention and treatment oflaryngeal cancer. Currently, the tumor biological target therapy is expected tohave a major breakthrough, and all scholars have focused their attention onfinding tumors with different gene targets, particularly characteristic andpathway targets，to provide a theoretical basis for clinical treatment. This kindof research is academically popular today. Therefore, this study aims to findthe expression of Keap1-Nrf2-ARE signaling pathway in supraglotticlaryngeal squamous cell carcinoma so as to explore its clinical significance.The abnormality of cell signal transduction and regulation is intimatelyrelated to the pathogenesis and growth of tumor, and the way in which thecancer can be treated through the intervention of signal transduction pathwayhas become a new field of biological treatment. The Keap1-Nrf2-ARE signaltransduction pathway plays an important role in the prevention of tumorformation and resistance to oxidative attack, and is also a crucial mechanismto defend carcinogen stimulation and maintain the balance of cell oxidationreduction. However, if this signaling pathway is destroyed, abnormality of cellsignal transduction and regulation will occur, leading to excess stimulation ofNrf2and overexpression of a variety of downstream genes. This will not only increase the sensitivity of cells to carcinogens and promote the growth ofcancer cells and the occurrence of cancer, but enhance the defense ability ofcancer cells.According to the study, Nrf2/Keap1signaling pathway discoveredrecently is constantly activated and found to abnormally modulate cells ingreat quantities of human tumors. It plays a vital role in the occurrence,development and evolution of human malignant tumor. However, the researchof the above signaling pathway in supraglottic laryngeal carcinoma has notbeen reported. Therefore, our study plans to use the immunohistochemicalmethod to evaluate the expressions of Nrf2, Keap1and ARE in supraglotticlaryngeal squamous cell carcinoma, and explore the relations and correlationsbetween these expressions and clinicopathological factors.Methods:The expressions of Nrf2, Keap1and ARE had been tested in the selected73cases of supraglottic carcinoma and12cases of normal laryngeal mucosaby using immunohistochemistry (MaxVision method).Results:1The expression of Keap1The positive staining of Keap1was located in the cytoplasm, and thelight yellow and dark brown stains were positive cells. The high expressionrate of Keap1in normal laryngeal mucosa was significantly higher than that insupraglottic squamous cell carcinoma (75.0%vs23.3%), and the differencewas statistically significant (P<0.05).The expression rate of Keap1in laryngeal carcinoma was closelycorrelated with the clinical stage: the later the clinical stage, the higher theexpression rate. The positive rate of Keap1in stage Ⅲ, Ⅳ laryngealcarcinoma cases (33.3%) was significantly higher than that of stage I, Ⅱlaryngeal carcinoma cases (9.7%, P<0.05). The expression of Keap1was notclearly correlated with age, sex, smoking history, tumor size, differentiationand lymph node metastasis (P>0.05)．2The expression of Nrf2 The positive staining of Nrf2was mostly located in the nucleus, partiallyin the cytoplasm, and appears yellowish brown or dark brown. The highexpression rate of Nrf2in supraglottic squamous cell carcinoma wassignificantly higher than that in normal laryngeal mucosa (53.4.0%vs16.7%,P<0.05).The high expression rates of Nrf2in poorly differentiated, moderatelydifferentiated, well differentiated carcinoma tissues were81.8%,45.5%and28.6%respectively, and the expression of Nrf2was inversely correlated withthe differentiation in supraglottic squamous cell carcinoma (P<0.05). The highexpression rate of Nrf2in the group with lymph node metastasis of cancer wassignificantly higher than those without lymph node metastasis (63.6%vs37.5%, P<0.05). However, Nrf2expression was not clearly correlated withage, sex of the patients, smoking history, tumor size and clinical stage(P>0.05).3The expression of AREThe positive staining of ARE was located in the nucleus, and theyellowish brown stains were positive cells. A few high expression rates ofARE can be seen in supraglottic squamous cell carcinoma and normallaryngeal mucosa tissues, and they were26.0%and33.3%respectively; andthe latter was higher than the former, but there was no statistical difference(P>0.05).ARE expression was not clearly correlated with differentiation, lymphnode metastasis, clinical stage, age, sex, smoking and tumor size (P>0.05)．4Relations between Nrf2, Keap1and AREThere was a negative correlation between the expressions of Nrf2andKeap1(r=-0.330, P=0.004); there was no correlation between Nrf2and ARE(r=0.116, P=0.330), and no correlation between Keap1and ARE (r=-0.313,P=0.792).Conclusion:1The abnormal Keap1-Nrf2-ARE signaling system was possiblyinvolved in the occurrence and progression of supraglottic laryngeal squamous cell carcinoma.2In supraglottic squamous cell carcinoma, the expression of Nrf2wasnegatively correlated with tumor differentiation, and positively correlated withlymph node metastasis.3In supraglottic squamous cell carcinoma, Keap1expression wascorrelated with TNM stage: the later the clinical stage, the stronger the Keap1expression.4A few high expression rates of ARE can be seen in supraglotticsquamous cell carcinoma and normal laryngeal mucosa, but the difference wasnot statistically significant.5There was a negative correlation between the expressions of Keap1andNrf2in supraglottic squamous cell carcinoma; there was no correlationbetween Nrf2and ARE, and no correlation between Keap1and ARE. |
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