关键词: 肺腺癌；lncRNA MALAT1；miR-181a-5p；JAK2/STAT3信号通路；病理特征；预后

Abstract: Objective To study the relationship between the expression of long non-coding RNA lung adenocarcinoma metastasis-associated transcript 1 (lncRNA MALAT1) and microRNA (miR)-181a-5p in lung adenocarcinoma tissues and the signal pathway of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3),clinicopathological features and prognosis.Methods 218 patients with lung adenocarcinoma who had surgical resection at our institution between January 2018 and May 2021 had their cancer tissues and nearby normal lung tissues collected,the levels of lncRNA MALAT1,miR-181a-5p and key factors of JAK2/STAT3 signaling pathway (JAK2 mRNA,STAT3 mRNA) in lung adenocarcinoma tissues and adjacent tissues were detected by reverse transcription polymerase chain reaction (RT-PCR).The correlation between the expression levels of lncRNA MALAT1 and miR-181a-5p in cancer tissues of lung adenocarcinoma patients and the levels of key factors in JAK2/STAT3 signaling pathway were analyzed by Pearson test.The relationship between the expression levels of lncRNA MALAT1 and miR-181a-5p and the clinicopathological features of lung adenocarcinoma patients were analyzed.Patients with lung adenocarcinoma were followed up for 3 years,and their prognosis was counted,the 3-year overall survival rate of lncRNA MALAT1 and miR-181a-5p low/high expression groups were analyzed by Kaplan-Meier method.The prognostic factors were analyzed by univariate and multivariate Cox risk proportional regression models.Results In lung adenocarcinoma tissues,the expression levels of lncRNA MALAT1,JAK2,and STAT3 mRNA were substantially greater (P<0.05) than in neighboring normal lung tissues,whereas the expression level of miR-181a-5p was significantly lower (P<0.05) in compared to nearby normal lung tissues.Pearson test results showed that,lncRNA MALAT1 was positively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=0.526、0.483),and miR-181a-5p was negatively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=-0.430、-0.493).lncRNA MALAT1 had a considerably greater expression rate and miR-181a-5p had a significantly lower expression rate in patients with TNM stage Ⅲa,lymph node metastasis and poorly differentiated lung adenocarcinoma than in patients with TNM stage Ⅰ-Ⅱ,without lymph node metastasis and moderately well differentiated lung adenocarcinoma (P<0.05).Three patients were lost during the 3-year follow-up of 218 patients with lung adenocarcinoma,and the 3-year overall survival rate was 58.14% (125/215).The 3-year overall survival rate of the lncRNA MALAT1 high expression group was considerably lower than that of the lncRNA MALAT1 low expression group.The miR-181a-5p high expression group had a substantially greater (P<0.05) .Lymph node metastasis,TNM stage Ⅲa,decreased expression level of miR-181a-5p,and increased expression level of lncRNA MALAT1 are risk factors for the prognosis of patients with lung adenocarcinoma(P<0.05).Conclusion The low expression of miR-181a-5p and the high expression of lncRNA MALAT1 in lung adenocarcinoma tissues are related to TNM stage IIIa,lymph node metastasis and poor prognosis,which may promote the progression of lung adenocarcinoma and cause poor prognosis by activating JAK2/STAT3 signaling pathway.

Key words: lung adenocarcinoma;lncRNA MALAT1;miR-181a-5p;JAK2/STAT3 signaling pathway;clinicopathological features;prognosis