Clinical Efficacy Observation Of Photodynamic Therapy Combined With In-situ Surgery For Difficult-to-treat BCC And Exploration Of Mechanism

Basal cell carcinoma(BCC)is the most common malignant tumor of the skin.One type of clinical classification,which is difficult to achieve complete remission with conventional treatment options,is called difficult-to-treat BCC.Mohs micrographic surgery(MMS)is the most commonly used treatment for difficult-to-treat BCC with good clinical prognosis.However,MMS is an expensive,time-consuming and labor-intensive technique.Photodynamic therapy(PDT),a new treatment option,is currently recommended only for low-risk superficial BCC patients in guidelines because its effective depth of treatment is only 2-4 mm.Thus difficult-to-treat BCC patients do not benefit from it.However,several studies have found that pretreatment can improve the efficacy of PDT by promoting better drug penetration and better protoporphyrin metabolism in the past decade,and that modified PDT may be suitable for difficult-to-treat BCC.PDT combined with in-situ surgery(ISS-PDT)improves the drug penetration while removing most of the primary lesions using in situ surgery.We compared the effectiveness and safety of ISS-PDT with the commonly used MMS treatment protocol.Additionally,we explored the differences in the expression of the peroxiredoxin family(Prdx)in BCC by biological prediction,single-cell sequencing,and immunohistochemistry,and mined the Prdx protein family molecules related to BCC occurrence,as well as comparing the expression level of relapsed and non-relapsed BCC tissues before treatment,to study the expression difference of Prdx in photodynamic therapy of BCC.Part Ⅰ Clinical efficacy observation of photodynamic therapy combined with in-situ surgery for difficult-to-treat basal cell carcinoma Objective: To observe the efficacy and safety of ISS-PDT for treating difficult-to-treat BCC and to compare it with MMS.Materials and Methods: Thirty-two patients were retrospectively included,of whom 48 lesions in 16 patients were treated with ISSPDT and 17 lesions in the other 16 patients were treated with MMS.The in situ procedures included in situ cutting and in situ resection procedures.Follow-up was at least 36 months after treatment,with controlled analyses of clinical efficacy,pre-and post-patient dermatologic quality-of-life index,cosmetic outcome,treatment time,healing time,treatment cost,and adverse effects.Results: There was one recurrence in the MMS group and no recurrence in the ISS-PDT group,with a median follow-up of 42.5months(36-63 months).There was no statistically significant difference in the recurrence rate between ISS-PDT and MMS(P=1.000).The mean healing time for ISS-PDT was 17.9 days,which was longer than the 7.5 days in the MMS group.Overall,the cosmetic outcome of ISS-PDT patients was not significantly different from that of MMS according to the cosmetic 4-point scale(P=0.719).Postoperative DLQI was significantly lower in both groups compared to the higher preoperative DLQI levels.Postoperative DLQI was better for ISS-PDT(Mean 0.88)than for MMS(Mean 3.44)[MD 2.56(95%CI 0.86 至 4.27);P=0.016].The median total treatment cost was (?)4330 for ISS-PDT and (?)6110 for MMS(P=0.003).Conclusion: PDT combined with in situ surgery is a safe,effective and aesthetic alternative to MMS for difficult-to-treat BCC in situations such as tumor size,specific location,number of lesions,patient’s own reasons(comorbidities,pacemakers,and advanced age),patient preference,etc.Part Ⅱ Exploration of the expression mechanism of Prdx family associated with PDT of BCC Objective:We explored the differential expression of the peroxiredoxin family(Prdx)in BCC by biological prediction,singlecell sequencing,and immunohistochemistry to uncover Prdx protein family molecules associated with BCC occurrence.By comparing the expression levels of relapsed and non-relapsed BCC tissues,the expression differences of Prdx in the efficacy of PDT for BCC were studied.Materials and Methods:Bioinformatics mRNA expression differential analysis was performed by Geodataset to explore the difference in the expression of RNAs in the Prdx protein family in normal and BCC tissues.Five BCC tissues and three of their paraneoplastic tissues were obtained for single-cell RNA sequencing(RNA-Seq)and data analysis,and further immunohistochemical validation analysis was performed in 10 normal tissues and 10 BCC tissues.Results:We found by bioinformatics that Prdx-1 and-3 of the RNAs of the Prdx protein family were differentially expressed in normal and BCC tissues;Prdx-1 expression was decreased in BCC tissues and Prdx-3 expression was elevated in BCC tissues.Single-cell RNA sequencing(RNA-Seq)analysis also showed decreased expression of Prdx-1 in BCC tissues and increased expression of Prdx-3 in BCC tissues.Other Prdx protein family molecules were not significantly different in normal and BCC tissues.Based on these results,our immunohistochemical analysis of Prdx-1 and Prdx-3 in normal and BCC tissues showed that Prdx-1 was mainly expressed negative or weakly positive in BCC tissues,and Prdx-3 was mainly expressed weakly positive or positive in BCC tissues.The expression of Prdx-1was mainly weakly positive or positive,and the expression of Prdx-3was mainly positive in the tissues which relapsed after PDT.Compared with the tissues which did not relapse after PDT,the expression intensity of Prdx-1 was increased,and the difference was statistically significant(P =0.04).There was no significant difference in expression intensity of Prdx-3(P =0.27).Conclusion:The down-regulation of Prdx-1 protein expression level and up-regulation of Prdx-3 protein expression levels may be associated with the development of BCC.After PDT treatment of BCC the strength of Prdx-1 expression may be closely related to whether BCC relapses.