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第42卷第3期                           南京医科大学学报(自然科学版)
                  2022年3月                   Journal of Nanjing Medical University(Natural Sciences)     ·317 ·


               ·基础研究·

                多肽组学分析揭示内源性多肽对肺腺癌恶性表型的关键作用



                孙重期 ,束永前 ,毛文君          2*
                              1
                      1
                南京医科大学第一附属医院肿瘤科,江苏 南京                  210029;南京医科大学附属无锡人民医院胸外科,江苏                 无锡   214023
                1                                            2


               [摘   要] 目的:通过多肽组学分析研究多肽在肺腺癌发生发展中的作用及潜在分子机制。方法:提取3对年龄匹配的男性
                肺腺癌组织和癌旁组织的内源性多肽,通过液相色谱⁃串联质谱法(liquid chromatography⁃tandem mass spectrometry,LC⁃MS/MS)
                筛选差异表达的多肽,借助生物信息学推测差异多肽的潜在功能,使用CCK⁃8实验、划痕实验、Transwell实验验证重点多肽对
                肺腺癌细胞株(A549、H1975)恶性表型的影响。结果:鉴定了10 kDa以下的多肽4 538条,共筛选出242条在癌组织和癌旁组
                织间存在差异表达的多肽(差异倍数≥2.0,FDR<0.05),对应202个前体蛋白。GO分析以及KEGG通路富集分析的结果显示这
                些蛋白与肿瘤发生发展的一系列重要生物学活动密切相关。聚焦于首次发现的多肽LACRP2,体外实验证实该多肽可以一定
                程度上抑制肺腺癌细胞株的恶性表型。结论:内源性多肽LACRP2可能与肺腺癌部分恶性表型有关。多肽组学可以更全面地
                帮助了解肺腺癌的发生发展机制。
               [关键词] 肺腺癌;多肽组学;恶性表型;分子机制
               [中图分类号] R734.2                   [文献标志码] A                       [文章编号] 1007⁃4368(2022)03⁃317⁃08
                doi:10.7655/NYDXBNS20220302



                Peptidomic analysis reveals the critical roles of endogenous peptides in the malignant
                phenotype of lung adenocarcinoma

                           1
                                         1
                SUN Chongqi ,SHU Yongqian ,MAO Wenjun 2*
                                                                                                      2
                1 Department of Oncology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;Department
                of Cardiothoracic Surgery,Wuxi People's Hospital Affiliated to Nanjing Medical University,Wuxi 214023,China

               [Abstract] Objective:This study aims to explore the role of peptides in lung adenocarcinoma and its potential molecular
                mechanisms through peptideomics analysis. Methods:Endogenous peptides from 3 pairs of age⁃matched male lung adenocarcinoma
                and paracancerous tissues were extracted and detected by liquid chromatography ⁃ tandem mass spectrometry(LC ⁃ MS/MS).
                Bioinformatics was used to infer the potential functions of differential peptides. CCK⁃8 assays,wound⁃healing assays,and Transwell
                assays were carried out to verify the effect of key peptides on the malignant phenotype of lung adenocarcinoma cell lines(A549,
                H1975). Results:A total of 4 538 peptides were identified,of which 242 were differentially expressed(fold change≥2.0,FDR<0.05),
                corresponding to 202 precursor proteins. GO analysis and KEGG pathway enrichment analysis showed that these proteins were closely
                related to a series of important biological activities of tumorigenesis and development. Additionally,the novel peptide LACRP2 was
                also focused on. It was confirmed that this peptide could inhibit some malignant phenotypes of lung adenocarcinoma cell lines in vitro.
                Conclusion:The endogenous peptide LACRP2 may be related to some malignant phenotypes of lung adenocarcinoma. Peptidomics can
                aid in understanding the pathogenesis of lung cancer more comprehensively.
               [Key words] lung adenocarcinoma;peptidomics;malignant phenotype;molecular mechanism
                                                                              [J Nanjing Med Univ,2022,42(03):317⁃324]




                    肺癌是全球范围内发病率第2以及死亡率最高                          界肺癌新发病例数为 220 万,占全部癌症病例的
                的恶性肿瘤,根据 2020 年全球癌症统计数据,全世                        11.4%,2020 年因肺癌死亡人数达到了 180 万,占总
                                                                                         [1]
               [基金项目] 国家自然科学基金(82003094)                          的癌症相关死亡的 18.0% 。其中,非小细胞肺癌
                ∗                                                (non⁃small cell lung cancer,NSCLC)占肺癌总数的
                通信作者(Corresponding author),E⁃mail:maowenjun1@126.com
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