Department of Clinic, School of Medicine, Yangzhou Polytechnic College.
Department of Nuclear Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Institute of Technology.
J Vis Exp. 2024 Aug 2(210). doi: 10.3791/65841.
The cytoskeleton plays an important role in platinum resistance in ovarian cancer. Tropomodulin 3 (TMOD3) is critical in the development of many tumors, but its role in the drug resistance of ovarian cancer remains unexplored. By analyzing data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, this study compared TMOD3 expression in ovarian cancer and normal tissues, and examined the expression of TMOD3 after platinum treatment in platinum-sensitive and platinum-resistant ovarian cancers. The Kaplan-Meier method was used to assess the effect of TMOD3 on overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients. microRNAs (miRNAs) targeting TMOD3 were predicted using TargetScan and analyzed using the TCGA database. Tumor Immune Estimation Resource (TIMER) and an integrated repository portal for tumor-immune system interactions (TISIDB) were used to determine the relationship between TMOD3 expression and immune infiltration. TMOD3 coexpression networks in ovarian cancer were explored using LinkedOmics, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and The Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics. The results showed that TMOD3 was highly expressed in ovarian cancer and was associated with the grading, staging, and metastasis of ovarian cancer. TMOD3 expression was significantly reduced in platinum-treated ovarian cancer cells and patients. However, TMOD3 expression was higher in platinum-resistant ovarian cancer cells and tissues compared to platinum-sensitive ones. Higher TMOD3 expression was significantly associated with lower OS and PFS in ovarian cancer patients treated with platinum-based chemotherapy. miRNA-mediated post-transcriptional regulation is likely responsible for high TMOD3 expression in ovarian cancer and platinum-resistant ovarian tissues. The expression of TMOD3 mRNA was associated with immune infiltration in ovarian cancer. These findings indicate that TMOD3 is highly expressed in ovarian cancer and is closely associated with platinum resistance and immune infiltration.
细胞骨架在卵巢癌的铂耐药中发挥重要作用。原肌球蛋白 3（TMOD3）在许多肿瘤的发展中至关重要，但它在卵巢癌耐药中的作用仍未被探索。通过分析来自基因表达综合数据库（GEO）、癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析联盟（CPTAC）数据库的数据，本研究比较了卵巢癌和正常组织中 TMOD3 的表达，并检测了铂敏感和铂耐药卵巢癌中 TMOD3 在铂治疗后的表达。Kaplan-Meier 方法用于评估 TMOD3 对卵巢癌患者总生存期（OS）和无进展生存期（PFS）的影响。使用 TargetScan 预测靶向 TMOD3 的 microRNAs（miRNAs），并使用 TCGA 数据库进行分析。使用肿瘤免疫估计资源（TIMER）和肿瘤-免疫系统相互作用综合资源库（TISIDB）来确定 TMOD3 表达与免疫浸润之间的关系。使用 LinkedOmics、搜索工具检索相互作用基因/蛋白（STRING）和注释、可视化和综合发现数据库（DAVID）生物信息学来探索卵巢癌中 TMOD3 的共表达网络。结果表明，TMOD3 在卵巢癌中高表达，并与卵巢癌的分级、分期和转移有关。TMOD3 在铂处理的卵巢癌细胞和患者中的表达显著降低。然而，与铂敏感的卵巢癌细胞和组织相比，铂耐药的卵巢癌细胞和组织中 TMOD3 的表达更高。TMOD3 表达较高与接受铂类化疗的卵巢癌患者的 OS 和 PFS 较低显著相关。miRNA 介导的转录后调控可能是导致卵巢癌和铂耐药卵巢组织中 TMOD3 高表达的原因。TMOD3 mRNA 的表达与卵巢癌中的免疫浸润有关。这些发现表明，TMOD3 在卵巢癌中高表达，与铂耐药和免疫浸润密切相关。
