| Background: According to statistics,cutaneous squamous cell carcinoma is the highest incidence of cutaneous malignancies in China,compared with other types of cutaneous cancer,it has a higher metastasis rate and a worse prognosis.Keratoacanthoma is a rare borderline tumor of the cutaneous.It's histological features are similar to those of cutaneous squamous cell carcinoma.It is very difficult to distinguish only by morphology,and the misdiagnosis rate is extremely high.Among the histological classification of WHO cutaneous tumors in the 2006 edition,keratoacanthoma are benign epithelial tumors,but in recent years some researchers have proposed that keratoacanthoma are a variant of cutaneous squamous cell carcinoma,and some cases can eventually develop into squamous cell carcinoma,which should be regarded as precancerous lesions of cutaneous squamous cell carcinoma or " keratoacanthoma type cutaneous squamous cell carcinoma ".In the latest(2018)classification criteria,keratoacanthoma is classified as highly differentiated squamous cell carcinoma,but the clinical definition of keratoacanthoma is still very controversial.The treatment and prognosis of these two types of tumors are very different.Most keratoacanthomas develop rapidly but can heal on their own,while skin squamous cell carcinomas grow slowly in the early stages and are not easy to detect.In the later stages,infiltration and metastasis of surrounding tissues often occur.So the differential diagnosis of the two is very important.At present,there is still a lack of highly specific identification markers in clinical pathology,which also increases the difficulty of the accuracy of treatment.Therefore,we hope to find important genes involved in regulating the occurrence of cutaneous squamous cell carcinoma,and determine whether it can be used as a molecular marker for identifying the two or a target therapy for the future by detecting the differential expression between cutaneous squamous cell carcinoma and keratoacanthoma.A large number of studies have found that signal transducer and activator of transcription(STAT)family genes play complex and important regulatory roles in physiological processes such as cell proliferation,apoptosis,differentiation,and immune regulation.The STATs gene can induce tumorigenesis by regulating the expression of various proto-oncogenes.The STAT3 was found to be up-regulated in various malignant tumors,but for cutaneous squamous cell carcinoma and keratoacanthoma,the expression of STATs gene and Whether the oncogene STAT3 is significantly different from cutaneous squamous cell carcinoma in borderline keratoacanthoma,there have been few related studies before.It has been reported that gene associated with retinoid-interferon mortality-19(GRIM-19)is an effective inhibitor of STAT3 activation,which can be directly combined with STAT3 to inhibit its activation and inhibit cell proliferation and promote apoptosis.However,in the pathogenesis of cutaneous squamous cell carcinoma,whether there is the regulation of the GRIM-19 / STAT3 axis,there have been few previous studies.This topic will focus on these issues.Objective 1.To detect the expression of tumor-associated genes STAT1,STAT3 and STAT5 in cutaneous squamous cell carcinoma and keratoacanthoma and whether they are related to the clinical characteristics of patients;2.Whether the expression of oncogene STAT3 in cutaneous squamous cell carcinoma and keratoacanthoma is statistically significant;3.In cutaneous squamous cell carcinoma and keratoacanthoma,the expression of GRIM-19 and whether it is related to the expression of STAT3.Methods 1.Use immunohistochemistry to detect the expression of STAT1,STAT3,STAT5 and GRIM-19 in cutaneous squamous cell carcinoma,keratoacanthoma and normal tissues and statistically analyze whether there is a correlation between the expression of each gene and each clinical feature of the patient;Then analyze whether there is a correlation between the expression of GRIM-19 and STAT3.2.Bioinformatics analysis was performed on the skin squamous cell carcinoma data set in the GEO,calculate the differences in STAT1,STAT3,STAT5 and GRIM-19 gene expression between cutaneous squamous cell carcinoma samples and normal control samples by paired t test;Then analyze the correlation between GRIM-19 and STAT3 gene expression.Results 1.Immunohistochemical results showed that p-STAT1 and p-STAT5(in the phosphorylated state)in the STAT family were negative in cutaneous squamous cell carcinoma and keratoacanthoma;the positive rate of p-STAT3 protein in cutaneous squamous cell carcinoma was 63.4%.And it was negatively correlated with the degree of differentiation(P=0.027,P<0.05),and had nothing to do with other clinical features;the positive rate in keratoacanthoma was 62.1%,which was not related to each clinical feature;2.The positive rate of p-STAT3 protein in cutaneous squamous cell carcinoma and keratoacanthoma was higher than that of normal tissues by 11.1%,and the difference was statistically significant(P<0.05);but p-STAT3 protein in cutaneous squamous cell carcinoma There was no significant difference with keratoacanthoma(P=0.909,P>0.05);3.The positive rate of GRIM-19 in cutaneous squamous cell carcinoma was 43.9%,and it was negatively correlated with tumor size(P=0.009,P<0.05),positively correlated with the degree of differentiation(P=0.028,P<0.05),but not related to other clinical characteristics;the positive rate in keratoacanthoma is 48.3%,and it is negatively correlated with the degree of malignant change(P=0.005,P<0.05),and has no relationship with other clinical characteristics;the positive rate in normal tissues is 61.1%,between the three There were no statistically significant differences in expression(P>0.05).4.In cutaneous squamous cell carcinoma,GRIM-19 was negatively correlated with p-STAT3 protein expression(r=-0.656,P=0.000,P<0.05);In keratoacanthoma,GRIM-19 was positively correlated with p-STAT3 protein expression(r = 0.471,P=0.010,P <0.05).5.The results of the GEO database show that STAT1,STAT3,and STAT5 a genes are significantly different in the cutaneous squamous cell carcinoma group and the normal control group(P<0.05);There is no difference in GRIM-19 gene expression between cutaneous squamous cell carcinoma group and normal control group(P>0.05),And there is no correlation between GRIM-19 and STAT3(r=0.2448,P=0.42,P>0.05)? Conclusion In cutaneous squamous cell carcinoma,the expression of STAT3 gene m RNA and protein are up-regulated,indicating that STAT3 gene is involved in the occurrence of cutaneous squamous cell carcinoma and plays a pro-cancer role.However,the expression of STAT3 protein between cutaneous squamous cell carcinoma and keratoacanthoma is not significant,and cannot be used as a differential diagnostic marker for the two.The expression of GRIM-19 m RNA and protein was not significantly different in cutaneous squamous cell carcinoma,keratoacanthoma and normal skin,and the correlation between GRIM-19 and STAT3 was poor.This shows that in cutaneous squamous cell tumors,the absence of GRIM-19 gene can inhibit the activation of STAT3 to play a tumor suppressive role,and the GRIM-19 / STAT3 axis may not participate in the molecular mechanism of cutaneous squamous cell carcinoma. |
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