Background/Objectives: To elucidate the differential transcriptional and intercellular signaling features of tumor components across various cancers, we conducted a comparative analysis using single-cell RNA sequencing (scRNA-seq). This technology enables detailed characterization of tumor ecosystems and may explain variations in tumor behavior among distinct cancer types.Methods: We analyzed publicly available scRNA-seq datasets (GEO) from seven cancer types—pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), breast cancer (BC), thyroid cancer (TC), gastric cancer (GC), and colorectal cancer (CRC)—to define their unique molecular characteristics and intercellular interactions.Results: PDAC displayed a distinct tumor microenvironment (TME) dominated by myeloid cells (~42%), including abundantCXCR1/CXCR2-expressing tumor-associated neutrophils (TANs) that preferentially interacted with immune rather than cancer cells. The competitive receptorACKR1was minimally expressed on endothelial cells, consistent with PDAC hypo-vascularity. In HCC, tumor cells lackedEPCAMand expressed complement and stem cell markers; cancer-associated fibroblasts (CAFs) were scarce, and stellate cells expressed the pericyte markerRGS5. CAFs were abundant in ESCC and BC, withIGF1/2expression, while in GC, these markers were uniquely found in plasma cells. Since BC and GC subtypes exhibit distinct TME patterns, it is necessary to perform subtype-specific analyses for these cancers. TC showed high expression of tumor-suppressor genes, includingHOPX, in tumor cells. Differential interactions and the presence of “dominant signaling cell populations “ with dominant outgoing signals may underlie the heterogeneity in tumor aggressiveness across these cancers.Conclusions: Comparative scRNA-seq analysis of multiple cancers reveals distinct tumor phenotypes and cell–cell communication patterns, offering insights into the molecular architecture of human solid tumors.
背景/目的：为阐明不同癌症类型中肿瘤成分的转录特征及细胞间信号传导差异，本研究采用单细胞RNA测序技术进行系统性比较分析。该技术能够精细解析肿瘤生态系统特征，或可解释不同癌症类型间肿瘤行为异质性的分子基础。 方法：通过分析七种癌症类型——胰腺导管腺癌、肝细胞癌、食管鳞状细胞癌、乳腺癌、甲状腺癌、胃癌和结直肠癌——的公共单细胞RNA测序数据集，系统解析其特异性分子特征与细胞间相互作用网络。 结果：胰腺导管腺癌呈现以髓系细胞为主导的独特肿瘤微环境，其中表达CXCR1/CXCR2的肿瘤相关中性粒细胞更倾向于与免疫细胞而非肿瘤细胞相互作用。内皮细胞中竞争性受体ACKR1的低表达与胰腺导管腺癌低血管化特征相符。肝细胞癌肿瘤细胞缺失EPCAM表达而呈现补体及干细胞标志物特征，癌症相关成纤维细胞稀少，星状细胞表达周细胞标志物RGS5。食管鳞状细胞癌与乳腺癌富含表达IGF1/2的癌症相关成纤维细胞，而胃癌中该标志物特异性地表达于浆细胞。鉴于乳腺癌与胃癌亚型呈现显著差异的肿瘤微环境特征，需开展亚型特异性分析。甲状腺癌肿瘤细胞中抑癌基因HOPX等高表达。差异化的细胞间相互作用及具有主导性输出信号的"优势信号细胞群"的存在，可能是导致这些癌症侵袭性异质性的潜在机制。 结论：多癌种单细胞RNA测序比较分析揭示了差异化的肿瘤表型与细胞通讯模式，为深入理解人类实体瘤的分子架构提供了新视角。
肿瘤(癌症)患者之家