PDF(Pubmed)
Abstract：
BACKGROUND: Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment and prediction of immunotherapy in bladder cancer (BLCA).
METHODS: In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital.
RESULTS: We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort.
CONCLUSIONS: Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.
METHODS: In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital.
RESULTS: We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort.
CONCLUSIONS: Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.
摘要：
背景：基底膜（BM）是细胞外基质的重要组成部分，在肿瘤细胞的生长和转移中起着重要作用。然而,基于BM的生物标志物很少被开发用于膀胱癌(BLCA)的预后评估和免疫治疗预测.
方法：在本研究中，我们使用BLCA公共数据库探讨BM相关基因(BMRGs)与预后的关系.使用共识聚类进行BLCA的新型分子分型。LASSO回归用于构建基于BMRGs的签名，并利用生存分析探讨其与预后的关系。进一步分析了关键的BMRG，以评估其临床特征和免疫前景。最后,采用免疫组织化学方法检测在我院接受手术或接受免疫检查点抑制剂(ICI)免疫治疗的BLCA患者hub基因的表达.
结果：我们全面分析了BMRGs与BLCA之间的关系，并建立了预后相关的特征，该特征对BLCA的预后预测具有独立影响。我们在公共数据库中进一步筛选和验证了关键基因MMP14。此外,我们发现,在我们的队列中,肌肉浸润性膀胱癌(MIBC)中MMP14表达显著较高,而高MMP14表达对ICI治疗的反应较差.
结论：我们的发现强调了BMRGs的令人满意的价值，并提示MMP14可能是预测BLCA预后和免疫治疗反应的潜在生物标志物。
方法：在本研究中，我们使用BLCA公共数据库探讨BM相关基因(BMRGs)与预后的关系.使用共识聚类进行BLCA的新型分子分型。LASSO回归用于构建基于BMRGs的签名，并利用生存分析探讨其与预后的关系。进一步分析了关键的BMRG，以评估其临床特征和免疫前景。最后,采用免疫组织化学方法检测在我院接受手术或接受免疫检查点抑制剂(ICI)免疫治疗的BLCA患者hub基因的表达.
结果：我们全面分析了BMRGs与BLCA之间的关系，并建立了预后相关的特征，该特征对BLCA的预后预测具有独立影响。我们在公共数据库中进一步筛选和验证了关键基因MMP14。此外,我们发现,在我们的队列中,肌肉浸润性膀胱癌(MIBC)中MMP14表达显著较高,而高MMP14表达对ICI治疗的反应较差.
结论：我们的发现强调了BMRGs的令人满意的价值，并提示MMP14可能是预测BLCA预后和免疫治疗反应的潜在生物标志物。
