Alfahed Abdulaziz
Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia.
Biology (Basel). 2024 Sep 24;13(10):753. doi: 10.3390/biology13100753.
The migration-proliferation dichotomy (MPD) has long been observed in cultured cancer cells. This phenomenon is not only relevant to tumour progression but may also have therapeutic significance in clinical cancer. However, MPD has rarely been investigated in primary cancer. This study aimed to either confirm or disprove the existence of MPD in primary cancer. Using primary gastric, colorectal and prostate cancer (GC, CRC and PCa) cohorts from the Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center, this study interrogated the MPD phenomenon by utilising RNA-Seq-based proliferation (CIN70 signature) and migration (epithelial-mesenchymal transition) indices, as well as gene set enrichment analyses (GSEA). Alternative hypothetical migration-proliferation models-The simultaneous migration-proliferation (SMP) and phenotype-refractory (PR) models-were compared to the MPD model by probing the migration-proliferation relationships within cancer stages and between early- and late-stage diseases using chi-square and independent T tests, z-score statistics and GSEA. The results revealed an inverse relationship between migration and proliferation signatures overall in the GC, CRC and PCa cohorts, as well as in early- and late-stage diseases. Additionally, a shift in proliferation- to migration dominance was observed from early- to late-stage diseases in the GC and CRC cohorts but not in the PCa cohorts, which showed enhanced proliferation dominance in metastatic tumours compared to primary cancers. The above features exhibited by the cancer cohorts are in keeping with the MPD model of the migration-proliferation relationship at the cellular level and exclude the SMP and PR migration-proliferation models.
迁移-增殖二分法（MPD）在培养的癌细胞中早已被观察到。这种现象不仅与肿瘤进展相关，在临床癌症中也可能具有治疗意义。然而，MPD在原发性癌症中很少被研究。本研究旨在证实或反驳原发性癌症中MPD的存在。利用来自癌症基因组图谱和纪念斯隆凯特琳癌症中心的原发性胃癌、结直肠癌和前列腺癌（GC、CRC和PCa）队列，本研究通过利用基于RNA测序的增殖（CIN70特征）和迁移（上皮-间质转化）指标以及基因集富集分析（GSEA）来探究MPD现象。通过使用卡方检验和独立t检验、z分数统计和GSEA，在癌症阶段内以及早期和晚期疾病之间探究迁移-增殖关系，将替代性的假设迁移-增殖模型——同时迁移-增殖（SMP）模型和表型难治（PR）模型——与MPD模型进行比较。结果显示，在GC、CRC和PCa队列中，以及在早期和晚期疾病中，迁移和增殖特征总体上呈负相关。此外，在GC和CRC队列中观察到从早期到晚期疾病，增殖优势向迁移优势的转变，但在PCa队列中未观察到，与原发性癌症相比，PCa队列在转移性肿瘤中显示出增强的增殖优势。癌症队列表现出的上述特征与细胞水平上迁移-增殖关系的MPD模型一致，排除了SMP和PR迁移-增殖模型。
