College of Life Sciences, Xinyang Normal University, Xinyang, China.
College of Life Medicine, Xinyang Normal University, Xinyang, China.
Cancer Rep (Hoboken). 2022 Sep;5(9):e1557. doi: 10.1002/cnr2.1557. Epub 2021 Sep 20.
Muscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment.
We aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer.
Gene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up-regulated genes and 2961 down-regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up-regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co-expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan-Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1, HIP1R, CFL2, TPM1, CSRP1, SYNM, POPDC2, PJA2, and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC.
The research suggests that CNKSR1, POPDC2, and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.
肌层浸润性膀胱癌（MIBC）是世界范围内常见的恶性肿瘤。由于其在预后和治疗反应方面存在异质性，因此能够预测生存或帮助 MIBC 患者做出治疗决策的生物标志物对于个体化治疗至关重要。
我们旨在整合生物信息学研究方法，以确定一组有效的生物标志物，用于预测、诊断和治疗 MIBC，为膀胱癌的诊断和治疗提供新的理论依据。
从癌症基因组图谱数据库下载 MIBC 的基因表达谱和临床数据。纳入了一个包含 129 例 MIBC 病例和对照的数据集。通过差异表达基因（DEG）分析，鉴定出 2084 个上调基因和 2961 个下调基因。然后，进行基因本体论分析，分别探讨 DEGs 的生物学功能。上调的 DEGs 主要富集在表皮细胞分化、有丝分裂核分裂等方面。它们还参与细胞周期、p53 信号通路、PPAR 信号通路等。加权基因共表达网络分析得到与病理分期和分级相关的五个模块，其中蓝色和绿松石色模块与 MIBC 最相关。接下来，使用 Kaplan-Meier 生存分析进一步识别与 MIBC 患者进展和预后相关的枢纽基因，筛选标准为 p 值 ≤ .05，我们发现与 MIBC 患者进展和预后相关的基因有 CNKSR1、HIP1R、CFL2、TPM1、CSRP1、SYNM、POPDC2、PJA2 和 RBBP8NL。最后，免疫组织化学实验进一步证实了 CNKSR1 在 MIBC 的肿瘤发生环境中发挥着重要作用。
该研究表明，CNKSR1、POPDC2 和 PJA2 可能是 MIBC 的新的治疗靶点生物标志物，特别是我们使用免疫组织化学进一步验证了 CNKSR1 作为 MIBC 的治疗靶点，这可能有助于改善 MIBC 的预后。
