环状RNA相关mRNA作为非吸烟女性肺腺癌预后因素的综合分析
Comprehensive Analysis of circRNA-Related mRNAs as Prognostic Factors in Non-Smoking Women with Lung Adenocarcinoma.
作者信息
Wang Hao, Wei Song, Wang Lijun, Zhang Zhihong
机构信息
Department of Respiratory Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, People's Republic of China.
Department of Respiratory Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, 230031, People's Republic of China.
出版信息
Int J Gen Med. 2024 Dec 3;17:5757-5771. doi: 10.2147/IJGM.S490478. eCollection 2024.
BACKGROUND
Non-smoking women with lung adenocarcinoma(NSWLA) is a significant health problem globally; the carcinogenesis and prognostic signature remain poorly understood. Circular RNAs (circRNAs) are gradually implicated in cancer formation through sponging miRNAs to regulate mRNAs.
METHODS
Tumor and paracancerous specimens from non-smoking women after lung adenocarcinoma surgery were collected for high-throughput sequencing of circRNA. miRNA and mRNA datasets were downloaded from TCGA. A circRNA-miRNA-mRNA network was built using differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs). Following that, GSEA was applied to analyze the biological function of mRNAs in the ceRNA network. Utilizing the mRNAs associated with prognosis, we created an original prognostic risk score model. The expression of DEmRNA in the ceRNA network was verified by mRNA-seq and scRNA-seq data (GSE131907). The expression of BTBD3 and EIF4EBP2 was then verified by immunohistochemistry.
RESULTS
16 pairs of adenocarcinoma tissues and their corresponding para-tumor samples were collected from thoracic surgery. We created a circRNA related ceRNA in NSWLA. The hsa_circ_0002346 regulation of the cancer cell proliferation may through the hsa_circ_0002346/miR-96-5p/EIF4EBP2 axis. Hsa_circ_0072309 may affect proliferation of lung adenocarcinoma and activate Nature Killer cells by targeting miR-32-5p to regulate PCMTD1 expression. Based upon mRNA (BTBD3, CFL2, EIF4EBP2, EVI5, PCMTD1, SYDE2) related to overall survival, we also created a predictive signature. According to mRNA-seq, scRNA-seq, and immunohistochemical data, the expression of BTBD3 and EIF4EBP2 was lower in tumor samples than in normal tissues nearby.
CONCLUSION
The circRNA related mRNAs played an important role in predicting the overall survival of NSWLA. The circRNA in the ceRNA network might unravel the pathogenesis and be potential novel targets for NSWLA.
背景
非吸烟女性肺腺癌（NSWLA）是全球一个重大的健康问题；其致癌机制和预后特征仍知之甚少。环状RNA（circRNA）通过充当微小RNA（miRNA）的海绵来调节信使RNA（mRNA），逐渐被认为与癌症形成有关。
方法
收集非吸烟女性肺腺癌手术后的肿瘤及癌旁组织标本进行circRNA高通量测序。miRNA和mRNA数据集从癌症基因组图谱（TCGA）下载。使用差异表达的circRNA（DEcircRNAs）、miRNA（DEmiRNAs）和mRNA（DEmRNAs）构建circRNA-miRNA-mRNA网络。随后，应用基因集富集分析（GSEA）来分析ceRNA网络中mRNA的生物学功能。利用与预后相关的mRNA，我们创建了一个原始的预后风险评分模型。通过mRNA测序和单细胞RNA测序数据（GSE131907）验证ceRNA网络中DEmRNA的表达。然后通过免疫组织化学验证BTBD3和EIF4EBP2的表达。
结果
从胸外科手术中收集了16对腺癌组织及其相应的癌旁样本。我们在NSWLA中创建了一个与circRNA相关的ceRNA。hsa_circ_0002346对癌细胞增殖的调控可能通过hsa_circ_0002346/miR-96-5p/EIF4EBP2轴。Hsa_circ_0072309可能通过靶向miR-32-5p调节PCMTD1表达来影响肺腺癌的增殖并激活自然杀伤细胞。基于与总生存相关的mRNA（BTBD3、CFL2、EIF4EBP2、EVI5、PCMTD1、SYDE2），我们还创建了一个预测指标。根据mRNA测序、单细胞RNA测序和免疫组织化学数据，肿瘤样本中BTBD3和EIF4EBP2的表达低于附近正常组织。
结论
与circRNA相关的mRNA在预测NSWLA的总生存中起重要作用。ceRNA网络中的circRNA可能揭示发病机制，是NSWLA潜在的新靶点。
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