Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Laboratory of Single Cell Biology, Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.
Sci Rep. 2024 Nov 1;14(1):26255. doi: 10.1038/s41598-024-76044-2.
Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. In this study, we performed spatial whole-transcriptome profiling of tongue cancer in young adults compared with older patients. Nine patients with tongue squamous cell carcinoma (T2-3N0-1M0) were included and divided into two groups: younger (n = 5) and older than 45 years (n = 4). Formalin-fixed paraffin-embedded (FFPE) and fresh frozen (FF) samples of tumor tissue from 4 young and 5 older patients, respectively, were used for spatial transcriptomic profiling using the 10 × Genomics Visium. The findings were validated using SeekGene single cell full-length RNA sequencing (1 young vs 1 older patient) and TCGA data (15 young vs 70 older patients). As a result, we performed the first successful integration of spatial transcriptomics data from FF and FFPE samples and revealed distinctive features of tongue cancer in young adults. Oxidative stress, vascular mimicry, and MAPK and JAK-STAT pathways were enriched in early-onset tongue cancer. Tumor microenvironment demonstrated increased gene signatures corresponding to myeloid-derived suppressor cells, tumor-associated macrophages, and plasma cells. The invasive front was accompanied by vascular mimicry with arrangement of tumor-associated macrophages and aggregations of plasma cells and lymphocytes organized into tertiary lymphoid structures. Taken together, these results indicate that early-onset tongue cancer has distinct transcriptomic features and molecular mechanisms compared to older patients.
年轻人的舌癌发病率、侵袭性和对治疗的反应较差。与头颈部肿瘤的经典病因学因素（如烟草、酒精和人乳头瘤病毒）无关的是，年轻人舌癌的发生。这种癌症的发展和进展机制仍不清楚。在这项研究中，我们对年轻和老年舌癌患者进行了空间全转录组分析。纳入了 9 名 T2-3N0-1M0 期舌鳞癌患者，分为年轻（n=5）和大于 45 岁（n=4）两组。分别从 4 名年轻患者和 5 名老年患者的肿瘤组织中采集福尔马林固定石蜡包埋（FFPE）和新鲜冷冻（FF）样本，使用 10× Genomics Visium 进行空间转录组分析。使用 SeekGene 单细胞全长 RNA 测序（1 名年轻患者和 1 名老年患者）和 TCGA 数据（15 名年轻患者和 70 名老年患者）验证了这些发现。结果成功地将 FF 和 FFPE 样本的空间转录组数据进行了首次整合，并揭示了年轻人舌癌的独特特征。氧化应激、血管模拟和 MAPK 和 JAK-STAT 途径在早期舌癌中富集。肿瘤微环境表现出与髓源性抑制细胞、肿瘤相关巨噬细胞和浆细胞相关的基因特征增加。侵袭前沿伴有血管模拟，肿瘤相关巨噬细胞和浆细胞聚集，并形成三级淋巴结构。综上所述，这些结果表明，与老年患者相比，早期舌癌具有明显的转录组特征和分子机制。
