Qi Zhaoyao, Gu Guoqing, Huang Huanwei, Lyu Beile, Liu Yibo, Wang Wei, Zha Xu, Liu Xicheng
Laboratory for Clinical Medicine, Beijing Key Laboratory for Tumor Invasion and Metastasis, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Laboratory for Clinical Medicine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Int J Mol Sci. 2025 Sep 22;26(18):9256. doi: 10.3390/ijms26189256.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. However, the spatial and temporal dynamics underlying its development remain poorly characterized. This study employs spatial transcriptomics (ST) to investigate the progression of intestinal tumors in mice across multiple time points. We identified distinct transcriptional profiles between tumor and normal tissues, resolving six major cell types through integrated dimensionality reduction and pathological annotation. Pseudo-time trajectory analysis revealed increased expression of and in later stages of tumor progression. Analysis of human CRC cohorts from the TCGA database further confirmed that high expression of these genes is associated with advanced clinical stages and promotes tumor proliferation and invasion. Temporal gene expression dynamics indicated enrichment of cancer-related pathways concurrent with suppression of lipid and amino acid metabolism. Notably, genes in the family were significantly upregulated in normal tissues compared to tumor tissues. Functional validation showed that inhibits colon cancer cell migration and proliferation in vitro. These demonstrate the value of ST in resolving spatiotemporal heterogeneity in CRC and identify both / and as potential biomarkers and therapeutic targets.
结直肠癌（CRC）仍然是全球癌症相关死亡的主要原因。然而，其发展背后的时空动态仍未得到充分表征。本研究采用空间转录组学（ST）来研究小鼠肠道肿瘤在多个时间点的进展。我们确定了肿瘤组织和正常组织之间不同的转录谱，通过综合降维和病理注释解析出六种主要细胞类型。伪时间轨迹分析显示，在肿瘤进展后期，[具体基因1]和[具体基因2]的表达增加。对来自TCGA数据库的人类CRC队列的分析进一步证实，这些基因的高表达与晚期临床阶段相关，并促进肿瘤增殖和侵袭。时间基因表达动态表明，癌症相关通路富集，同时脂质和氨基酸代谢受到抑制。值得注意的是，与肿瘤组织相比，[基因家族名称]家族中的基因在正常组织中显著上调。功能验证表明，[具体基因]在体外抑制结肠癌细胞的迁移和增殖。这些结果证明了ST在解析CRC时空异质性方面的价值，并确定了[具体基因1] / [具体基因2]作为潜在的生物标志物和治疗靶点。
