背景与目的:非小细胞肺癌(non-small cell lung cancer, NSCLC)是目前全球发病率最高和死亡人数最多的恶性肿瘤,而其具体的发病机制仍然未知。相关文献和既往实验研究发现m6A的阅读蛋白YTHDF2可能通过分子之间的相互作用抑制NSCLC的发...背景与目的:非小细胞肺癌(non-small cell lung cancer, NSCLC)是目前全球发病率最高和死亡人数最多的恶性肿瘤,而其具体的发病机制仍然未知。相关文献和既往实验研究发现m6A的阅读蛋白YTHDF2可能通过分子之间的相互作用抑制NSCLC的发生、发展。本研究拟通过对NSCLC患者肿瘤组织进行病理观察以及生信分析,探索NSCLC的发生发展机制,对未来产生更加有效的NSCLC治疗手段和改善NSCLC患者的预后提供参考。方法:回顾性收集2021年5月至2022年5月于青岛大学胸外科确诊肺癌并住院手术的64例NSCLC患者的肿瘤及癌旁组织(根据世界卫生组织形态学标准)。对上诉样本分别进行病理染色及生信分析。结果:64例标本的HE染色可见肿瘤组织中病理损伤明显,能明确采集样本的诊断并与癌旁组织区分。TUNEL染色可见:肿瘤组织细胞凋亡水平升高。qRT-PCR实验结果表明在肿瘤组织中YTHDF2和p14基因表达水平明显高于癌旁组织(P ARF蛋白的表达,达到延缓NSCLC发生、发展和改善NSCLC患者预后的作用。Background and objective: Non-small cell lung cancer (NSCLC) is currently the most prevalent and deadly malignancy worldwide. However, the precise mechanisms underlying its pathogenesis remain largely unknown. Previous literature and experimental studies suggest that YTHDF2, an m6A reader protein, may inhibit the initiation and progression of NSCLC through molecular interactions. This study aims to explore the mechanisms involved in the development and progression of NSCLC by conducting pathological observations and bioinformatic analyses of tumor tissues from NSCLC patients. The findings are expected to contribute to the development of more effective treatment strategies for NSCLC and to improve the prognosis of NSCLC patients. Methods: We retrospectively collected tumor and adjacent normal tissues from 64 NSCLC patients who were diagnosed and underwent surgery between May 2021 and May 2022 in the Department of Thoracic Surgery at Qingdao University, following the World Health Organization (WHO) morphological criteria. Pathological staining and bioinformatic analyses were performed on the collected samples. Results: Hematoxylin and eosin staining of the 64 specimens revealed significant pathological damage within the tumor tissue, which could clearly diagnose the collected samples and distinguish them from the adjacent tissues. TUNEL staining showed that the level of apoptosis in tumor tissues was increased compared with adjacent tissues. The results of qRT-PCR showed that the expression levels of YTHDF2 and p14 genes in tumor tissues of NSCLC patients were significantly higher than those in adjacent tissues (P ARF protein expression. It can delay the occurrence and development of NSCLC and improve the prognosis of NSCLC patients.展开更多
背景与目的:YTH基因家族的所有成员都属于m6A阅读蛋白,负责参与肿瘤发生发展过程中的甲基化调控。然而,YTH基因家族在肝癌中的表达情况和具体作用仍有待进一步阐明。本文旨在通过生物信息学方法探究YTH家族成员在肝癌中的表达与预后价值...背景与目的:YTH基因家族的所有成员都属于m6A阅读蛋白,负责参与肿瘤发生发展过程中的甲基化调控。然而,YTH基因家族在肝癌中的表达情况和具体作用仍有待进一步阐明。本文旨在通过生物信息学方法探究YTH家族成员在肝癌中的表达与预后价值,及其与免疫浸润及相关功能的关系。方法:用UALCAN数据库分析YTH基因家族在肝癌及其亚组中的表达差异。采用Kaplan-Meier plotter数据库分析YTH基因家族在肝癌中的预后价值。使用c Bio Portal数据库进行YTH基因家族的共表达谱和遗传学变异分析。通过Web Gestalt数据库进行YTH基因家族的功能和通路富集分析。YTH基因家族与肝癌中的免疫细胞浸润的相关性分析采用TIMER 2.0数据库完成。结果:肝癌中YTHDC1、YTHDC2、YTHDF1、YTHDF2、YTHDF3的m RNA表达均较正常肝组织明显升高,并与临床TNM分期及肿瘤分级密切相关,其在1、2、3期/级中表达逐级升高,而在4期/级中表达水平下降。预后分析显示,YTHDF1和YTHDF2的高表达均与患者更短的总生存期(OS)和无复发生存期(RFS)明显相关。TCGA数据库和c Bio Portal工具分析显示,YTHDF3基因变异率为25%,是YTH家族中最高的。GO功能富集分析显示YTH基因家族的主要癌症相关功能指向代谢及生物合成分解方向,尤其是激素代谢、固醇类代谢、脂代谢、药物分解代谢等。通过TIMER 2.0数据库分析多数YTH家族成员的表达与CD4^(+)T细胞、CD8^(+)T细胞、B细胞、中性粒细胞以及树突细胞的浸润呈正相关,与巨噬细胞浸润呈负相关。结论:YTH基因家族在肝癌中存在分子和表达谱的失调。YTH基因家族成员(尤其是YTHDF1和YTHDF2)是肝癌潜在的预后标志物和新的治疗靶点,这些发现可为肝癌机制与靶向治疗的研究提供新的途径。展开更多
文摘背景与目的:非小细胞肺癌(non-small cell lung cancer, NSCLC)是目前全球发病率最高和死亡人数最多的恶性肿瘤,而其具体的发病机制仍然未知。相关文献和既往实验研究发现m6A的阅读蛋白YTHDF2可能通过分子之间的相互作用抑制NSCLC的发生、发展。本研究拟通过对NSCLC患者肿瘤组织进行病理观察以及生信分析,探索NSCLC的发生发展机制,对未来产生更加有效的NSCLC治疗手段和改善NSCLC患者的预后提供参考。方法:回顾性收集2021年5月至2022年5月于青岛大学胸外科确诊肺癌并住院手术的64例NSCLC患者的肿瘤及癌旁组织(根据世界卫生组织形态学标准)。对上诉样本分别进行病理染色及生信分析。结果:64例标本的HE染色可见肿瘤组织中病理损伤明显,能明确采集样本的诊断并与癌旁组织区分。TUNEL染色可见:肿瘤组织细胞凋亡水平升高。qRT-PCR实验结果表明在肿瘤组织中YTHDF2和p14基因表达水平明显高于癌旁组织(P ARF蛋白的表达,达到延缓NSCLC发生、发展和改善NSCLC患者预后的作用。Background and objective: Non-small cell lung cancer (NSCLC) is currently the most prevalent and deadly malignancy worldwide. However, the precise mechanisms underlying its pathogenesis remain largely unknown. Previous literature and experimental studies suggest that YTHDF2, an m6A reader protein, may inhibit the initiation and progression of NSCLC through molecular interactions. This study aims to explore the mechanisms involved in the development and progression of NSCLC by conducting pathological observations and bioinformatic analyses of tumor tissues from NSCLC patients. The findings are expected to contribute to the development of more effective treatment strategies for NSCLC and to improve the prognosis of NSCLC patients. Methods: We retrospectively collected tumor and adjacent normal tissues from 64 NSCLC patients who were diagnosed and underwent surgery between May 2021 and May 2022 in the Department of Thoracic Surgery at Qingdao University, following the World Health Organization (WHO) morphological criteria. Pathological staining and bioinformatic analyses were performed on the collected samples. Results: Hematoxylin and eosin staining of the 64 specimens revealed significant pathological damage within the tumor tissue, which could clearly diagnose the collected samples and distinguish them from the adjacent tissues. TUNEL staining showed that the level of apoptosis in tumor tissues was increased compared with adjacent tissues. The results of qRT-PCR showed that the expression levels of YTHDF2 and p14 genes in tumor tissues of NSCLC patients were significantly higher than those in adjacent tissues (P ARF protein expression. It can delay the occurrence and development of NSCLC and improve the prognosis of NSCLC patients.
文摘背景与目的:YTH基因家族的所有成员都属于m6A阅读蛋白,负责参与肿瘤发生发展过程中的甲基化调控。然而,YTH基因家族在肝癌中的表达情况和具体作用仍有待进一步阐明。本文旨在通过生物信息学方法探究YTH家族成员在肝癌中的表达与预后价值,及其与免疫浸润及相关功能的关系。方法:用UALCAN数据库分析YTH基因家族在肝癌及其亚组中的表达差异。采用Kaplan-Meier plotter数据库分析YTH基因家族在肝癌中的预后价值。使用c Bio Portal数据库进行YTH基因家族的共表达谱和遗传学变异分析。通过Web Gestalt数据库进行YTH基因家族的功能和通路富集分析。YTH基因家族与肝癌中的免疫细胞浸润的相关性分析采用TIMER 2.0数据库完成。结果:肝癌中YTHDC1、YTHDC2、YTHDF1、YTHDF2、YTHDF3的m RNA表达均较正常肝组织明显升高,并与临床TNM分期及肿瘤分级密切相关,其在1、2、3期/级中表达逐级升高,而在4期/级中表达水平下降。预后分析显示,YTHDF1和YTHDF2的高表达均与患者更短的总生存期(OS)和无复发生存期(RFS)明显相关。TCGA数据库和c Bio Portal工具分析显示,YTHDF3基因变异率为25%,是YTH家族中最高的。GO功能富集分析显示YTH基因家族的主要癌症相关功能指向代谢及生物合成分解方向,尤其是激素代谢、固醇类代谢、脂代谢、药物分解代谢等。通过TIMER 2.0数据库分析多数YTH家族成员的表达与CD4^(+)T细胞、CD8^(+)T细胞、B细胞、中性粒细胞以及树突细胞的浸润呈正相关,与巨噬细胞浸润呈负相关。结论:YTH基因家族在肝癌中存在分子和表达谱的失调。YTH基因家族成员(尤其是YTHDF1和YTHDF2)是肝癌潜在的预后标志物和新的治疗靶点,这些发现可为肝癌机制与靶向治疗的研究提供新的途径。