RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
直肠癌活检的定量分析：数字病理分割算法 QuantCRC 与治疗反应和复发相关
英文原题：Quantitative Analysis of Rectal Cancer Biopsies With the Digital Pathology Segmentation Algorithm QuantCRC Associates With Therapy Response and Recurrence.
查看英文原题
Quantitative Analysis of Rectal Cancer Biopsies With the Digital Pathology Segmentation Algorithm QuantCRC Associates With Therapy Response and Recurrence.
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中文摘要
我们研究了QuantCRC这一数字病理分割算法在直肠癌治疗前活检中是否与新辅助治疗的病理完全缓解（pCR）、无复发生存期（RFS）以及转录组空间分析相关。QuantCRC在一个由288例治疗前活检组成的观察性队列和一个由37例接受新辅助治疗的直肠腺癌患者治疗前活检组成的独立验证队列中进行了评估。QuantCRC特征与临床结局、pCR和RFS之间的关联分别采用多变量logistic回归和Cox比例风险模型进行分析。QuantCRC变量还与37例cT3N+直肠癌治疗前活检的转录组数字空间分析进行了相关性分析。QuantCRC得出的每平方毫米肿瘤上皮淋巴细胞（TIL（肿瘤浸润淋巴细胞）[TILs]）与pCR显著相关（多变量比值比，1.05；95% CI，1.02-1.10；P = .038）。在达到pCR的治疗前活检中，QuantCRC得出的TILs显著更高（91.3 vs 55.9 lymphocytes/mm 2；P = .004）。
验证队列证实，只有直肠癌治疗前活检中QuantCRC得出的TILs与新辅助治疗的完全缓解显著相关。QuantCRC %高肿瘤分级与更差的RFS独立相关（多变量风险比，1.27；95% CI，1.09-1.47；P = .002）。QuantCRC识别出的高肿瘤分级≥10.1%的患者RFS显著降低（5年RFS 69% vs 83%，log-rank P = .007）。转录组分析发现，免疫细胞内高白细胞介素（IL）-6/JAK/STAT3信号传导与更差的RFS相关（校正P = .01）。免疫细胞内 IL-6/JAK/STAT3 低表达的肿瘤与高表达的肿瘤相比，TILs 显著更高（中位数，152 vs 97 TILs/mm 2；P = .039）。活检适配的 QuantCRC 在治疗前直肠癌中可能有助于识别达到 pCR 且有复发风险的患者。
展开英文摘要原文
We examined whether QuantCRC, a digital pathology segmentation algorithm, on pretherapy rectal cancer biopsies is associated with pathologic complete response (pCR) to neoadjuvant therapy, recurrence-free survival (RFS), and transcriptomic spatial profiling. QuantCRC was evaluated in an observational cohort of 288 pretherapy biopsies and a separate validation cohort of 37 pretherapy biopsies of rectal adenocarcinoma from patients undergoing neoadjuvant therapy. Associations between QuantCRC features and clinical outcomes, pCR, and RFS were analyzed using multivariable logistic regression and Cox proportional hazards modeling, respectively. QuantCRC variables were also correlated with transcriptomic digital spatial profiling of 37 pretreatment biopsies of cT3N + rectal cancer. QuantCRC-derived lymphocytes per square millimeter of tumor epithelium (tumor-infiltrating lymphocytes [TILs]) was significantly associated with pCR (multivariate odds ratio, 1. 05; 95% CI, 1. 02-1. 10; P = . 038).
QuantCRC-derived TILs were significantly higher in pretherapy biopsies with pCR (91. 3 vs 55. 9 lymphocytes/mm 2 ; P = . 004). The validation cohort confirmed that only QuantCRC-derived TILs in pretherapy biopsies of rectal cancer were significantly associated with complete response to neoadjuvant therapy. QuantCRC %high tumor grade was independently associated with worse RFS (multivariate hazards ratio, 1. 27; 95% CI, 1. 09-1. 47; P = . 002). Patients with ≥10. 1% high tumor grade identified by QuantCRC had significantly reduced RFS (5-year RFS 69% vs 83%, log-rank P = .
007). Transcriptomic profiling identified high interleukin (IL)-6/JAK/STAT3 signaling within immune cells to be associated with worse RFS (adjusted P = . 01). Tumors with low IL-6/JAK/STAT3 expression within immune cells had significantly higher TILs compared with tumors with high expression (median, 152 vs 97 TILs/mm 2 ; P = . 039). Biopsy-adapted QuantCRC in pretherapy rectal cancer may be helpful in identifying patients who achieve pCR and are at risk for recurrence.
论文信息
- 作者
- Pai RK、Eslinger C、Lee K、Farchoukh LF、Walden D、Emiloju O、Storandt M、Hagen CE
- 单位
- Department of Pathology, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: pair@upmc.edu.United States
- 文献类型
- 观察性研究
- 期刊
- Laboratory investigation; a journal of technical methods and pathology2025 Aug
- 原文标识
- PubMed 40311875 · DOI 10.1016/j.labinv.2025.104187