论文题名(中文): | 光线性角化病的光动力治疗及lncRNA-mRNA共表达网络的初步研究 |
姓名: | |
论文语种: | chi |
学位: | 硕士 |
学位类型: | 专业学位 |
学校: | 北京协和医学院 |
院系: | |
专业: | |
指导教师姓名: | |
校内导师组成员姓名(逗号分隔): | |
论文完成日期: | 2022-05-16 |
论文题名(外文): | Photodynamic therapy and lncRNA-mRNA co-expression network in Actinic Keratosis |
关键词(中文): | |
关键词(外文): | actinic keratosis photodynamic therapy efficiency mRNA lncRNA |
论文文摘(中文): |
目的: 1、比较全面部ALA-PDT与单皮损ALA-PDT治疗AK的清除率和复发率。 2、评估液氮冷冻联合全面部ALA-PDT治疗AK的疗效及安全性。 3、探讨lncRNA-mRNA共表达在AK中的作用机制。 方法: 1、采用随机、单盲研究方法,将AK患者分为两组,A组:全面部ALA-PDT组;B组:单皮损ALA-PDT组。治疗频率为每7-10天1次,疗程为2-3次。记录每次治疗后的皮损清除率及不良反应。末次治疗后3个月、6个月、1年对患者进行随访,记录复发率。主要疗效指标为末次治疗后3个月、6个月患者总AK皮损的完全清除率(CR率)、部分清除率(PR率)、无反应率(NR率);末次治疗后3个月、6个月、1年复发率。 2、招募AK患者,进行液氮冷冻联合全面部ALA-PDT治疗,治疗频率为每7-10天1次,疗程为2-3次,记录每次治疗后的皮损清除率及不良反应。末次治疗后3个月、6个月对患者进行随访,记录复发率。与全面部ALA-PDT组比较清除率和复发率,主要疗效指标为末次治疗后3个月、6个月患者患者总AK病变的CR、PR、NR率。 3、将AK患者皮损组织和正常人皮肤组织进行mRNA、lncRNA微阵列分析,对差异表达基因行GO和KEGG富集分析,最后建立mRNA-lncRNA共表达网络。 结果: 1、共纳入26例患者进行全面部或者单皮损ALA-PDT,每组13例,平均年龄68.23±8.93岁,AK皮损总数为246个。治疗3个月后,两组的CR率分别为82.4%和78.1%;PR率分别为17.6%和21.9%。治疗6个月后,两组CR率分别为81.4%和77.5%,PR率分别为18.6%和22.5%。两组NR率均为0。治疗3个月、6个月两组CR、PR均无显著统计学差异。治疗3个月、6个月后,两组复发率分别为0,18.2%和0,50%,无明显统计学差异。但在治疗1年后,A组复发率显著低于B组(分别为18.2%和62.4%,P<0.05)。治疗3个月后,Ⅱ级皮损CR率分别为66.7%和70.0%,Ⅲ级皮损CR率分别为46.2%和45.5%,均明显低于Ⅰ级皮损CR率(分别为91.2%和90.5%)。最常见的不良反应是红斑和疼痛,两组间的不良反应、患者治疗和美容效果满意度均无明显差异。 2、纳入13例患者进行冷冻联合全面部ALA-PDT,平均年龄73.92±9.54岁,AK病变总数为239个。治疗3个月后,总病变CR率为90.0%,PR率为10.0%,6个月后,CR率为90.0%,PR率为10.0%,清除率均明显高于单纯全面部ALA-PDT组(90.0% Vs 82.4%,90.0% Vs 81.4%,P<0.05)。对于不同等级AK皮损,治疗3个月后联合治疗组的CR率分别为Ⅰ级97.2%,Ⅱ级84.4%,Ⅲ级57.1%,均高于单纯全面部ALA-PDT组(Ⅰ/Ⅱ/Ⅲ级皮损CR率分别为91.2%,66.7%,46.2%),其中Ⅱ级AK皮损CR率具有显著统计学差异(P<0.05)。治疗3个月、6个月后,联合治疗组的复发率较单纯ALA-PDT无显著统计学差异。最常见的不良反应是红斑和疼痛,但较单纯全面部ALA-PDT,不良反应、患者治疗和美容效果满意度均无统计学差异。 3、2例AK皮损样本和3例正常皮肤样本共检测到36612个lncRNA和32255个mRNA,其中2097个lncRNA和2043个mRNA在两组间具有统计学差异,832个lncRNA和1315个mRNA显著上调,1265个lncRNA和728个mRNA显著下调。uc011fnr.2为AK中最显著下调的lncRNA,与14个mRNA有共表达关系,包括USB1、OASL、UBASH3A、SCIMP等。GO分析表明,相比于正常皮肤组织,AK中共有7773个GO术语在生物过程中、735个GO术语在分子功能中和1541个GO术语在细胞成分中差异表达。KEGG通路分析显示差异RNA在282条KEGG通路显著富集,其中TLR信号通路为明显富集差异mRNA的通路。 结论: 1、全面部ALA-PDT和单皮损ALA-PDT治疗AK在清除率上无明显差异。但在治疗1年后,全面部ALA-PDT能显著减少复发的风险,且不会增加不良反应的发生。 2、液氮冷冻联合全面部ALA-PDT适用于Ⅱ级等肥厚型AK皮损,增加其清除率的同时不会增加治疗不良反应,且有较好的美容效果。 3、uc011fnr.2可能通过负调节SCIMP、TLR4、IL-6分子,抑制JAK-STAT3信号通路,从而对AK的发生发展起到保护作用,uc011fnr.2可能成为AK未来的生物标志物之一。 关键词:光线性角化病;光动力治疗;疗效;mRNA;lncRNA |
论文文摘(外文): |
Objectives: 1. To compare the clearance and recurrence rates of full-face ALA-PDT and lesion-by-lesion ALA-PDT in the treatment of AK. 2. To evaluate the clinical efficacy and safety of cryotherapy combined with full-face ALA-PDT in the treatment of AK. 3. To explore the mechanism of mRNA-lncRNA co-expression network in AK. Methods: 1. This was a single-blind randomized study. AK patients were divided into two groups. Group A: full-face ALA-PDT group; Group B: lesion-by-lesion ALA-PDT group. All AK patients received PDT once every 7-10 days and about 2-3 times. The patients were followed up 3 months, 6 months and 1 year after the last treatment. 2. AK patients were treated by cryotherapy combined with full-face ALA-PDT. All AK patients received PDT once every 7-10 days and about 2-3 times. The patients were followed up 3 months and 6 months after the last treatment. 3. AK samples and normal skin tissue samples were collected from patients, and the mRNA and lncRNA microarray were analyzed by using RNA chip. GO and KEGG analysis were used to predict potential functional involvement of mRNA and lncRNA. Finally, mRNA-lncRNA co-expression analysis was used to clarify the relationship. Results: 1. 26 patients were enrolled in this study, average age was 68.23±8.93 years. The total number of AK lesions was 246. After 3 months, CR rates in Group A and Group B were 82.4% and 78.1% respectively; PR rates were 17.6% and 21.9%. After 6 months, CR rates in Group A and Group B were 81.4% and 77.5% respectively, PR rates were 18.6% and 22.5%. The NR rates were 0 in both groups. There were no significant differences in CR rate and PR rate between two groups (P>0.05). The recurrence rates of Group A were significantly lower than those of Group B after 1 year (18.2% Vs 62.4%, P<0.05). The response rates and recurrence rates were different according to the AK grades. The most common adverse events were erythema and pain. There were no significant differences in adverse events and patient satisfaction regarding treatment or cosmetic outcome between two groups. 2. 13 patients were enrolled in this study, average age was 73.92±9.54 years. The total number of AK lesions was 239. After 3 months, CR rate and PR rate were 90.0% and 10.0%, and after 6 months, was 90.0% and 10.0%, which were both significantly higher than full-face group (90.0% Vs 82.4%, 90.0% Vs 81.4%, P<0.05). For different grades of AK lesions, After 3 months, the CR rates of combination group were 97.2% (grade Ⅰ), 84.4% (grade Ⅱ), 57.1% (grade Ⅲ), which were both significantly higher than full-face group (91.2%, 66.7%, 46.2%, P<0.05). After 3 and 6 months, the recurrence rates were no significant differences between the two groups (P>0.05). The most common adverse events during the treatment were erythema and pain. There were no significant differences in adverse events and patient satisfaction regarding treatment or cosmetic outcome between two groups. 3. Based on the results of RNA-sequencing data, the results showed that the expression of 2097 lncRNA and 2043 mRNAs was found to be significantly changed,Among these, 832 lncRNA and 1315 mRNA were significantly upregulated and 1265 lncRNA and 728 mRNA were significantly downregulated in AK. uc011fnr.2 was the most significantly downregulated lncRNA in AK, which is co-expressed with 14 mRNAs, including USB1, OASL, SCIMP, UBASH3A and etc. GO analysis showed that a total of 7773 GO terms in biological processes, 735 in molecular functions, and 1541 in cellular components were differentially expressed in AK. The KEGG pathway analysis show that 282 KEGG pathways significantly enriched with the differentially expressed mRNAs, TLR signal pathway was the pathway that significantly enriched differential mRNA. Conclusions: 1. There were no significant differences in the clinical efficacy of full-face ALA-PDT group and lesion-by-lesion ALA-PDT group in the treatment of AK. However, after 1 year of the last treatment, full-face group could reduce the recurrence risk of AK and would not increase the occurrence of adverse events. 2. Cryotherapy combined with full-face ALA-PDT had great clearance rate and safety, especially suitable for grade Ⅱ and other hypertrophic AK, and would not increase the adverse events of treatment. The cosmetic outcome was excellent. 3. lncRNA uc011fnr.2 may play an important role in JAK-STAT3 signaling pathway of AK by modulating SCIMP, TLR4 and IL-6, protecting the occurrence and development of AK, uc011fnr.2 may become one of the biomarkers of AK in the future. Key words: actinic keratosis; photodynamic therapy; efficiency; mRNA;lncRNA |
开放日期: | 2022-05-24 |