CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
自我认同的非洲血统与结肠和直肠腺癌全切片图像中病理组学衍生的 TIL（肿瘤浸润淋巴细胞）评分：一项探索性多队列全切片图像研究
英文原题：Self-identified African ancestry and pathomics-derived tumor-infiltrating lymphocyte scores in colon and rectal adenocarcinoma whole-slide images: an exploratory multicohort whole-slide image study.
查看英文原题
Self-identified African ancestry and pathomics-derived tumor-infiltrating lymphocyte scores in colon and rectal adenocarcinoma whole-slide images: an exploratory multicohort whole-slide image study.
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研究概要
这些初步结果凸显了在公开可获取数据集中扩大少数群体代表性的必要性。
研究思路结论见上方概要
AI辅助计算的苏木精和伊红（H&E）染色全切片图像（WSI）中TIL（肿瘤浸润淋巴细胞）百分比（TIL%）评分，可作为对患者进行免疫检查点抑制剂治疗分层的有效生物标志物。
为验证自我认定的非洲血统（AA）与欧洲血统（EA）相比与更高的TIL%评分相关的假设，WSI由三个多样化的福尔马林固定石蜡包埋（FFPE）结肠和直肠腺癌（COAD-READ）肿瘤组织队列组装而成：1）从癌症基因组图谱（TCGA）-COAD-READ数据库下载的242例AA vs. EA WSI；2）从三个美国医疗中心收集的97例独立的美国自我认定AA vs. EA WSI；3）从单一尼日利亚医疗中心收集的48例（共51例）尼日利亚WSI。TCGA队列中有33例适合分析的自我认定AA WSI，美国队列中有49例自我认定AA WSI。对于TCGA队列，从与FFPE样本一起收集的平行冷冻肿瘤样本中生成了241例全转录组RNA测序数据。对于美国队列，从与WSI相同的FFPE块中生成了87例外显子组捕获富集的RNA-seq数据。
在合并的 TCGA 和美国 AA 队列与尼日利亚队列之间，未检测到中位 TIL% 评分的差异。对合并的 TCGA 和美国队列进行的探索性多元回归分析显示，在控制 MMR/MSI 状态和其他协变量后，AA 具有更高的 TIL% 评分（估计差异 = 3.01%，95% CI（0.54%，5.49%），P 值 = 0.0170）。然而，由于 TCGA 和美国队列在自我认同为 AA 的代表性方面存在差异，这一结果需要谨慎解读。在模型中对队列进行调整后，AA 与更高 TIL% 评分的关联不再显著（估计差异 = 2.05%，95% CI（-0.59%，4.70%），P 值 = 0.1277）。在分别分析的 TCGA 和美国队列中，检测到计算的 TIL% 评分与 CIBERSORTx 估计的淋巴细胞和 T 细胞丰度之间存在中度相关性。在 TIL% 评分与 CXCL10 和 CCL5 基因表达值之间也检测到中度相关性。
展开英文摘要原文
To test the hypothesis that self-identified African ancestry (AA) vs. European ancestry (EA) was associated with higher TIL% scores, WSI were assembled from three diverse cohorts of formalin-fixed paraffin embedded (FFPE) colon and rectal adenocarcinoma (COAD-READ) tumor tissues: 1.) 242 AA vs. EA WSI downloaded from The Cancer Genome Atlas (TCGA)-COAD-READ database; 2.) 97 independent US self-identified AA vs. EA WSI assembled from three US medical centers; 3.) 48 (of 51) Nigerian WSI assembled from a single Nigerian medical center. There were 33 self-identified AA WSI suitable for analysis in the TCGA cohort and 49 self-identified AA WSI in the US cohort. For the TCGA cohort, 241 whole transcriptome RNA-sequence data were generated from parallel frozen tumor samples collected alongside the FFPE samples. For the US cohort, 87 RNA-seq enriched by exome capture data were generated from the same FFPE blocks as WSI.
No difference in median TIL% scores was detected between the combined TCGA and US AA cohorts and the Nigerian cohort. Exploratory multiple regression analysis of the combined TCGA and US cohorts revealed that AA had a higher TIL% score (Estimated difference = 3.01%, 95% CI (0.54%, 5.49%), P-value = 0.0170), while controlling for MMR/MSI status and other covariates. However, this result needs to be interpreted with caution because of differences between the TCGA and US cohorts with respect to representation of self-identified AA. After adjustment for cohort in the model, the association of AA with a higher TIL% score was no longer significant (Estimated difference = 2.05%, 95% CI(-0.59%, 4.70%), P-value = 0.1277). Moderate correlations were detected in the TCGA and US cohorts analyzed separately between computed TIL% scores and CIBERSORTx estimates of lymphocyte and T-cell abundance. Moderate correlations were also detected between TIL% scores and CXCL10 and CCL5 gene expression values.
These preliminary results underscore the need for expanding the representation of minority populations in publicly accessible datasets.
论文信息
- 作者
- Zhang Y、Cheng X、Liao Y、Adams S、Joseph DF、Flores RE、LaComb JF、Clark JM
- 单位
- Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, United States.United States
- 期刊
- Frontiers in oncology2026
- 原文标识
- PubMed 42638859 · DOI 10.3389/fonc.2026.1855135
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