Huang Rui, Wang Fuhao, Zou Wenxue, Li Xiaohui, Lei Tianyu, Li Peihang, Song Yajun, Liu Chao, Yue Jinbo
Department of Oncology, Chongqing University Fuling Hospital, Chongqing, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical Universityand, Shandong Academy of Medical Sciences , Jinan, China.
Biomark Res. 2024 Sep 18;12(1):106. doi: 10.1186/s40364-024-00655-0.
Podocalyxin-like protein (PODXL) is known to originate from tumor cells in several cancers; however, which cell type it is expressed in, whether and how it may contribute to tumor progression after radiotherapy or chemoradiotherapy in cervical cancer (CC) remain unknown. In this study, we investigated these issues using a cohort of 180 immune stain data, single-cell RNA sequencing (scRNA-seq) data of 29,453 cells, and bulk RNA sequencing data from 187 cervical cancer samples treated with radiotherapy or chemoradiotherapy. ScRNA-seq analysis revealed that PODXL was predominantly expressed in tumor endothelial cells (TECs) of CC, which was corroborated by tumor section staining. Moreover, the PODXL expression level was negatively associated with progression-free survival and overall survival of 180 CC patients receiving radiotherapy or chemoradiotherapy (both p < 0.001). Furthermore, compared with PODXL TECs, PODXL TECs exhibited a diminished anti-tumor immune response and enhanced tumor-promoting features characteristics. In addition, PODXL over-expression was also found to be negatively associated with immune response and indicated poor survival in bulk RNA sequencing data of CC treated with radiotherapy or chemoradiotherapy. These results underscore the role of PODXL in CC, suggesting it as a promising target and prognostic marker for patients treated with radiotherapy or chemoradiotherapy.
已知足细胞毒素样蛋白（PODXL）源自多种癌症的肿瘤细胞；然而，在宫颈癌（CC）中它在何种细胞类型中表达、放疗或放化疗后它是否以及如何促进肿瘤进展仍不清楚。在本研究中，我们使用180例免疫染色数据、29453个细胞的单细胞RNA测序（scRNA-seq）数据以及187例接受放疗或放化疗的宫颈癌样本的批量RNA测序数据来研究这些问题。scRNA-seq分析显示PODXL主要在CC的肿瘤内皮细胞（TEC）中表达，肿瘤切片染色证实了这一点。此外，PODXL表达水平与180例接受放疗或放化疗的CC患者的无进展生存期和总生存期呈负相关（均p < 0.001）。此外，与非PODXL TEC相比，PODXL TEC表现出抗肿瘤免疫反应减弱和促肿瘤特征增强。另外，在接受放疗或放化疗的CC批量RNA测序数据中还发现PODXL过表达也与免疫反应呈负相关，并表明生存期较差。这些结果强调了PODXL在CC中的作用，表明它是接受放疗或放化疗患者的一个有前景的靶点和预后标志物。
