解码肿瘤微环境和分子机制：通过单细胞 RNA 测序和批量 RNA 测序分析揭示宫颈癌亚群和预后特征。

BACKGROUND: Cervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated. METHODS: We utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes. RESULTS: Through our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator-the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines. CONCLUSION: This study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches.

背景：宫颈癌（CC）是一种常见的妇科肿瘤，近年来，年轻人群中的发病率明显上升。然而，CC 的内在细胞异质性仍未得到充分研究。

方法：我们利用单细胞 RNA 测序（scRNA-seq）转录组分析，仔细研究了来自 4 名宫颈癌（CC）患者的肿瘤上皮细胞。这种方法能够鉴定肿瘤上皮细胞的关键亚群，并阐明它们对 CC 进展的贡献。随后，我们评估了在 Bulk RNA-seq（Bulk RNA-seq）队列中相关分子的影响，并进行了细胞实验验证。

结果：通过分析，我们发现 C3 PLP2+肿瘤上皮祖细胞是宫颈癌（CC）中的一个重要亚群，对 CC 的分化和进展起着关键作用。我们建立了一个独立的预后指标——PLP2+肿瘤 EPCs 评分。根据中位数评分将患者分为高、低评分组，我们发现高评分组的生存率明显低于低评分组。这些组与免疫浸润、富集途径、单核苷酸多态性（SNP）、药物敏感性等因素之间的相关性进一步表明它们对 CC 预后的影响。细胞实验验证了 ATF6 对 CC 细胞系增殖和迁移的显著影响。

结论：本研究丰富了我们对决定 CC 进展的因素的认识，提高了对 CC 肿瘤微环境的认识，并为未来的 CC 治疗提供了有价值的见解。这些发现有助于完善 CC 的诊断，并制定最佳的治疗方法。