肿瘤细胞治疗研究
英文原题：Tumor microenvironment-based classification for predicting gastric cancer prognosis.
利用 TSR 和 TIL 将胃癌分为三种肿瘤微环境亚型，为生存预测提供了可靠的预后工具。
背景：肿瘤微环境（TME）由肿瘤相关间质和TIL（肿瘤浸润淋巴细胞）构成，对胃癌（GC）预后评估至关重要，但其常规临床应用仍有限。方法：研究纳入 320 例 GC 患者，对苏木精-伊红染色切片进行虚拟染色和图像处理，定量评估肿瘤-间质比（TSR）和 TIL，并基于单变量 Cox 回归评分系统建立 TME 预测模型 TME PATH。根据模型将患者分组以预测生存，并通过基因组分析关联 TME 预后模型与特定基因改变。结果：根据最大化总生存预测一致性指数的 0.76 截点，将 TSR 分为低组（n = 113）和高组（n = 207）。根据 0.03 截点定义两种 TIL 亚型。整合 TSR 和 TIL 亚型的复合生物标志物 TME PATH 将患者分为低危组 91 例（28.4%）、中危组 167 例（52.2%）和高危组 62 例（19.4%），与生存结局相关（中危对低危 HR 1.281；95% CI 0.957–1.714；高危对低危 HR 1.768；95% CI 1.242–2.517；log-rank P = 0.0061）。在另一队列（n = 186）中验证了这些结果，且具有显著临床意义（中危对低危 HR 1.389；95% CI 0.855–2.257；高危对低危 HR 2.435；95% CI 1.380–4.298；log-rank P = 0.0064）。TSR、TIL 和 TME PATH 与微卫星不稳定性、肿瘤突变负荷及 CDH1 突变相关。结论：使用 TSR 和 TIL 将 GC 分为 3 种 TME 亚型，可提供可靠的生存预后工具。
BACKGROUND: The tumor microenvironment (TME), consisting of tumor-associated stroma and tumor-infiltrating lymphocytes (TIL), is crucial for prognostic information in gastric cancer (GC). Despite its potential, routine clinical adoption remains limited. METHODS: In a study of 320 GC patients, virtual staining and image processing were applied to hematoxylin & eosin-stained slides. This method quantified the tumor-stroma ratio (TSR) and TIL, leading to a TME-based prediction model (TME PATH ) using a scoring system derived from univariate Cox regression. Subgroups were categorized to predict GC patient survival, with genomic analysis linking TME-based prognostic models to specific genetic alterations. RESULTS: TSR was categorized into TSR_low (n = 113) and TSR_high (n = 207) using a 0.76 cut-off, selected to maximize the concordance index for overall survival prediction. Two TIL subtypes were defined based on a 0.03 cut-off. TME PATH, a composite biomarker integrating the TSR- and TIL-based subtypes, stratified patients into low-risk (91 patients, 28.4 %), medium-risk (167 patients, 52.2 %), and high-risk (62 patients, 19.4 %) groups, correlating with survival outcomes (hazard ratio [HR] 1.281; 95 % CI 0.957-1.714 for medium vs. low-risk, and HR 1.768; 95 % CI 1.242-2.517 for high vs. low-risk; log-rank P = 0.0061). These findings were validated in a separate cohort (n = 186) with significant clinical relevance (HR 1.389; 95 % CI 0.855-2.257 for medium vs. low-risk, and HR 2.435; 95 % CI 1.380-4.298 for high vs. low-risk; log-rank P = 0.0064). TSR, TIL, and TME PATH were associated with microsatellite instability, tumor mutation burden, and CDH1 mutations. CONCLUSION: The classification of GC into three TME subtypes using TSR and TIL provides a reliable prognostic tool for survival prediction.
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