The Expression And Significance Of PKD1 And Its Phosphorylation Sites In Squamous Cell Carcinoma,Bowen’s Disease And Actinic Keratosis

Background and Objective:Cutaneous squamous cell carcinoma is a malignant proliferative disease that originated in epidermis or appendage keratinocytes,and the incidence rate of cutaneous non-melanin malignant tumors is the second.Actinic keratosis、Bowen’s disease and skin squamous cell carcinoma are stratified squamous cell-derived skin lesions.AK is a precancerous lesion of SCC,BD is an in situ squamous cell carcinoma,and both can progress to SCC and are invasive.They All occur in the exposed parts of the body with a considerable degree of suffering,affecting the quality of life of patients.With the advent of an aging society,the elderly population increased the incidence of various chronic diseases showed an increase in the corresponding increase in skin tumors.From precancerous disease,in situ squamous cell carcinoma to invasive squamous cell carcinoma is a multi-stage multi-factor involved in the complex process,the specific link between the three and need to be more in-depth exploration.PKD1 is the most important members of the calcium / calmodulin-dependent serine /threonine kinase D family.It is widely expressed in various tissues and organs playing an important role in regulating a series of cellular biological behaviors and maintaining cellular functions.The PKD1 gene(also known as PRKD1)is located on the human chromosome 14q11 site and is expressed abnormally in a variety of tumor tissues.It has been confirmed that PRKD1 gene is abnormally expressed in skin malignant tumors such as basal cell carcinoma and melanoma,with an important impact on theepidemal epidermal keratinocyte proliferation and differentiation.Most studies have shown that the role of PKD1 on cells through its own regulation of phosphorylation,the most important two phosphorylation sites are Ser916 and Tyr463.PKD1,p-PKD1-Tyr463 and p-PKD1-Ser916 were detected by gene and protein level in SCC,BD,AK and normal epidermis in order to investigate the role and significance of PKD1 in the gradual formation and development of skin squamous cell carcinoma.Methods:1.The expression of PRKD1 m RNA in SCC group,BD group,AK group and normal control group was detected by real-time quantitative PCR,to analysis the differences in expression.2.PKD1,p-PKD1-Tyr463,p-PKD1-Ser916 protein in the samples of SCC,BD,AK and normal controls were detected by Western blot.3.The expression of PKD1 and its phosphorylation sites p-PKD1-Tyr463,p-PKD1-Ser916 in SCC,BD,AK and normal controls were detected by immunohistochemical staining in the specific location of the tissue.Results:1.The expression of PRKD1 m RNA in normal skin tissues,SCC,BD and AK tissues were 0.64 ± 0.09,5.37 ± 1.06,2.96 ± 0.72 and 2.43 ± 0.46,the difference of PRKD1 m RNA expression between the four groups was statistically significant(F = 21.37,P <0.05).The expression of PRKD1 m RNA in SCC was 8.4 times higher than that in normal group,and the expression of PKD1 m RNA in SCC was also significantly higher than that in BD and AK(P <0.05),and there was no significant difference between BD and AK Meaning(P> 0.05).2.The expression of PKD1 in the squamous cell carcinoma and squamous cell carcinoma(CMS)was significantly higher than that innormal control tissues(χ2BD = 4.29,χ2SCC = 12.96,All P <0.01).The expression of PKD1 in SCC group increased with the increase of pathological grade of squamous cell carcinoma.There was no significant difference between AK group and normal control group(χ2 = 1.20,P>0.05).p-PKD1-Ser916 was only expressed in a small part of the well-differentiated SCC,but was not statistically significant compared with the normal group(Fisher exact test,P> 0.05),but not in poorly differentiated squamous cell carcinoma expression.p-PKD1-tyr463 was only expressed in SCC and BD tissues,and there was no significant difference between the two groups(χ2 = 1.69,P> 0.01).There was a positive correlation between PKD1 and its phosphorylation site Tyr463 in the SCC group(rcc = 0.479,P <0.05).3.PKD1 and its phosphorylation sites Ser916 and Tyr463 in the expression of immunohistochemical results in line with the general trend.With GAPDH as the internal reference protein,PKD1 was highly expressed tissues,whereas p PKD1Ser916 was low in all tissues.Conclusion:1.PKD1 and its phosphorylation site tyr463 were highly expressed in skin squamous cell carcinoma and in situ squamous cell carcinoma,and the total protein of PKD1 increased with the pathological grade of squamous cell carcinoma.2.PKD1 and its phosphorylation site Tyr463 may be involved in the development of squamous epithelium-derived cutaneous tumors.PKD1 may play a catalytic role in the process of skin squamous cell carcinogenesis through the activation of Tyr463 sites,Cell carcinoma of the new target.