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
CDX2 表达状态与 TIL（肿瘤浸润淋巴细胞）密度联合作为辅助 FOLFOX 治疗 III 期结直肠癌患者的预后因素
英文原题：The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers.
查看英文原题
The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers.
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研究概要
CD8 iTIL 的高密度总体上并未使 CDX2 缺失的结直肠癌（CRC）患者的生存出现差异。
中文摘要
背景
尾型同源框 2（CDX2）丢失的结直肠癌（CRC）具有侵袭性，但往往伴随较高的TIL（肿瘤浸润淋巴细胞）密度。然而，CDX2 丢失与 TIL 密度是否相互作用并影响 CRC 患者生存，所知甚少。
方法
采用免疫组化评估 III 期 CRC 组织中的 CDX2 丢失，并通过基于机器学习的分析方法，评估上皮内区（iTIL）和间质区 CD8 TIL 密度。
结果
CDX2 丢失与上皮内和间质区 CD8 TIL 密度较高均显著相关。CDX2 丢失和高 CD8 iTIL 密度均为预后指标，对癌症特异性生存的风险比分别为 2.314（1.050–5.100）和 0.378（0.175–0.817）。保留 CDX2 表达且 CD8 iTIL 密度高的 CRC 亚组临床结局最佳（风险比 0.138 [0.023–0.826]）；而 CDX2 丢失且 CD8 iTIL 密度高的亚组结局最差（风险比 15.781 [3.939–63.230]）。
结论
总体而言，CD8 iTIL 密度高并未改善 CDX2 丢失 CRC 患者的生存。对于接受辅助化疗的 III 期 CRC 患者，CDX2 表达与上皮内 CD8 TIL 密度的组合是独立预后标志物。
展开英文摘要原文
BACKGROUND
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
METHODS
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
RESULTS
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050-5.100) and 0.378 (0.175-0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023-0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939-63.230]).
CONCLUSIONS
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
论文信息
- 作者
- Lee JA、Park HE、Jin HY、Jin L、Yoo SY、Cho NY、Bae JM、Kim JH
- 第一作者单位
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.South Korea
- 通讯作者单位
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.South Korea
- 期刊
- Journal of pathology and translational medicine2025 Jan
- 原文标识
- PubMed 39440351 · DOI 10.4132/jptm.2024.09.26
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