狗口腔状细胞癌的空间转录基因景观
Stephanie Goldschmidt1, Clifford G Tepper2, Jack Goon3
1Department of Surgical & Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Molecular carcinogenesis
|June 17, 2025
概括
这项研究绘制了狗口腔状细胞癌 (COSCC) 转录组的地图,揭示了瘤区域和微环境中的独特分子特征. 结果确定了恶性瘤和治疗点的潜在生物标志物,为人类癌症比较研究提供了见解.
科学领域:
- 兽医瘤学 兽医瘤学
- 比较病理学比较病理学
- 癌症基因组学 癌症基因组学
背景情况:
- 狗口腔状细胞癌 (COSCC) 是狗中普遍存在的瘤,是人类口腔癌研究的宝贵模型.
- 以前对COSCC的基因组研究依赖于批量测序,限制了空间和分子分辨率.
- 了解COSCC的转录组景观对于识别生物标志物和治疗点至关重要.
研究的目的:
- 以空间分辨率全面分析COSCC的转录形态景观.
- 为了比较瘤区域的分子特征,周围瘤发育不良,和瘤微环境与正常的口腔组织.
- 确定恶性瘤和治疗点的潜在生物标志物.
主要方法:
- 对COSCC样本进行空间转录学分析,包括表面瘤,深入入侵性瘤,周围瘤形上皮质和瘤微环境.
- 与匹配的正常口腔样本进行比较.
- 基因组丰富分析和差异表达基因的识别.
主要成果:
- 在COSCC的不同区域观察到不同的分子特征.
- 与上皮生长因子 (EGFR) 和上皮-介质细胞转化 (EMT) 相关的基因在皮质变形和表面癌症中被上调.
- 鉴定出了异形性病变 (FZD4,GAS1,HACD2,NOG,SLC39A6) 和侵入性COSCC (SFRP4,FZD1,IL34) 的特定基因特征.
- 瘤微环境显示巨细胞,IL-10分泌和CD4+T细胞表达刺激性 (ICOS) 和抑制性 (CTLA4) 分子的增加,表明免疫抑制.
结论:
- 这项研究提供了COSCC的详细的转录基因地图,突出了区域分子差异.
- 鉴定出来的基因有可能成为恶性瘤的生物标志物,预测瘤行为,以及新的治疗点.
- 免疫调节性瘤微环境,特别是高CTLA4表达,表明抗瘤免疫反应被抑制,这需要进一步调查.
相关概念视频
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...