研究概要
子宫内膜癌(EC)是最常见的妇科恶性肿瘤之一。
中文摘要
子宫内膜癌(EC)是最常见的妇科恶性肿瘤之一。尽管其发病率较高,但Sonic Hedgehog(SHH)通路等分子通路在EC背景下尚未得到广泛研究。本研究旨在探讨SHH表达在EC中的临床意义,有望揭示该疾病发病机制的新见解,并为EC的治疗策略提供有价值的参考。我们利用癌症基因组图谱(TCGA)的数据,根据SHH通路相关基因衍生的基因特征评分,将数据集分为“高SHH”和“低SHH”组。我们探索了这些组的临床和肿瘤特征,重点关注关键癌症标志,包括干性、增殖、细胞溶解活性、肿瘤微环境和基因组不稳定性。“高SHH”肿瘤作为一个独特的类别,具有有利的临床和分子特征。这些肿瘤表现出较低的增殖率、减少的血管生成和降低的基因组不稳定性,表明其肿瘤生长模式受控且侵袭性较低。此外,“高SHH”肿瘤显示出较低的干性,突出了其侵袭性较低的表型。“高SHH”肿瘤的免疫微环境富含免疫细胞类型,如巨噬细胞M0、单核细胞、B细胞、CD8 T细胞、CD4 T细胞、滤泡辅助T细胞和NK 细胞。这种免疫富集,加上较高的细胞溶解活性,提示抗肿瘤免疫反应增强。我们的研究揭示了Sonic信号在EC中的临床意义。“高SHH”肿瘤表现出独特的分子和临床特征,与有利的癌症标志、较低的分级和更好的生存相关。这些发现强调了SHH表达作为稳健预后生物标志物的潜在效用,为EC的个体化治疗策略提供了宝贵见解。理解SHH通路在EC中的作用有助于加深我们对这种癌症的认识,并可能为未来更有效的治疗策略铺平道路。
展开英文摘要原文
Endometrial Cancer (EC) is one of the most common gynecological malignancies. Despite its prevalence, molecular pathways, such as the Sonic Hedgehog (SHH) pathway, have not been extensively studied in the context of EC. This study aims to explore the clinical implications of SHH expression in EC, potentially uncovering new insights into the disease's pathogenesis and offering valuable insights for therapeutic strategies in EC. We utilized data from The Cancer Genome Atlas (TCGA) to divide the dataset into ' High SHH ' and ' Low SHH ' groups based on a gene signature score derived from SHH pathway-related genes. We explored the clinical and tumor characteristics of these groups, focusing on key cancer hallmarks, including stemness, proliferation, cytolytic activity, tumor micro-environment, and genomic instability. ' High SHH ' tumors emerged as a distinct category with favorable clinical and molecular features. These tumors exhibited lower proliferation rates, reduced angiogenesis, and diminished genomic instability, indicating a controlled and less aggressive tumor growth pattern. Moreover, ' High SHH ' tumors displayed lower stemness, highlighting a less invasive phenotype. The immune micro-environment in ' High SHH ' tumors was enriched with immune cell types, such as macrophage M0, monocytes, B cells, CD8 T cells, CD4 T cells, follicular helper T cells, and natural killer cells. This immune enrichment, coupled with higher cytolytic activity, suggested an improved anti-tumor immune response. Our study sheds light on the clinical significance of Sonic signaling in EC. ' High SHH ' tumors exhibit a unique molecular and clinical profile associated with favorable cancer hallmarks, lower grades, and better survival. These findings underscore the potential utility of SHH expression as a robust prognostic biomarker, offering valuable insights for tailored therapeutic strategies in EC. Understanding the SHH pathway's role in EC contributes to our growing knowledge of this cancer and may pave the way for more effective treatment strategies in the future.
论文信息
- 作者
- Snijesh VP、Krishnamurthy S、Bhardwaj V、Punya KM、Niranjana Murthy AS、Almutadares M、Habhab WT、Nasser KK
- 第一作者单位
- Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore 560034, Karnataka, India.India
- 通讯作者单位
- Department of Science, Prince Sultan Military College of Health Sciences, Dhahran 31932, Saudi Arabia.Saudi Arabia
- 期刊
- International journal of molecular sciences2024 Sep 27