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
英文原题:Higher Levels of Tumour-Infiltrating Lymphocytes (TILs) are Associated with a Better Prognosis, While CDK5 Plays a Different Role Between Nonmetastatic and Metastatic Colonic Carcinoma.
Higher Levels of Tumour-Infiltrating Lymphocytes (TILs) are Associated with a Better Prognosis, While CDK5 Plays a Different Role Between Nonmetastatic and Metastatic Colonic Carcinoma.
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CDK5 高表达提示非转移性结肠癌预后良好,而在转移性结肠癌中则相反,且 CDK5 的表达与 TILs 无关。
在真实人群队列中评估结肠癌患者细胞周期蛋白依赖性激酶5(CDK5)的预后价值。
对296例结肠癌组织进行免疫组化,回顾分析CDK5表达。采用卡方检验、Kaplan-Meier和Cox回归比较不同表达水平以及转移/非转移患者结局;同时测定TIL数量并分析其预后关系。
296例中CDK5阴性18例(6.09%)、弱阳性77例(26.01%)、中度阳性124例(41.89%)、强阳性77例(26.01%)。CDK5表达与错配修复状态或TIL无关。非转移患者中,CDK5高表达(2+或3+)者PFS及癌症特异生存(CSS)较低表达者更长;转移性患者中方向相反(p<0.001)。226例有TIL评估,低TIL 115例(50.88%),高TIL 111例(49.12%)。TIL比例>0.2者CSS和PFS显著更好。多变量分析中高TIL是CSS保护因素,但未达显著(HR 0.59,95% CI 0.33–1.06,p=0.079),PFS也未显著。
CDK5高表达提示非转移结肠癌预后好,但转移癌中相反,且与TIL无关。高TIL患者预后较好,结肠癌适宜截点为20%。
We investigated the prognostic value of cyclin-dependent kinase 5 (CDK5) in a true population-based cohort of patients with colon cancer.
1. Immunohistochemical (IHC) staining was used to retrospectively analyse the expression of CDK5 in colon cancer tissue samples of 296 patients. The 2 test, Kaplan-Meier method and Cox proportional regression model were used to analyse the difference between the patients with differential expression of CDK5 and with different stages (metastatic and nonmetastatic); 2. The number of tumour-infiltrating lymphocytes (TILs) in tumour sections was determined, and its relationship with prognosis was explored.
1. Among 296 patients stained for CDK5, 18 cases (6.09%) showed negative expression, 77 cases (26.01%) showed weak expression (+1), 124 cases (41.89%) showed medium positive expression (2+), and 77 cases (26.01%) showed strong positive expression (3+). The expression of CDK5 was neither related to mismatch repair nor TILs ( p > .05 ). In non-metastatic patients, longer progression-free survival (PFS) and cancer-specific survival (CSS) were observed in patients with high CDK5 expression (2+ or 3+) than low CDK5 expression (- or 1+), while in metastatic disease, the opposite was true ( p < .001 ). 2. TILs in 226 patients were detected in the study. Among them, 115 cases (50.88%) showed a low number of TILs (TILs-L), and 111 cases (49.12%) showed a high number of TILs (TILs-H). Patients with a TIL ratio greater than .2 had a significantly better CSS ( p < .001 ) or PFS ( p = .008 ) than patients with a lower TIL ratio. By multivariate analysis, TILs-H was a protective factor for CSS, however failed to reach a significant difference (hazard ratio: .59, 95% CI: .33 1.06, p = .079 ), and so was the PFS (HR: .65, 95% CI: .29 1.43, p = .279 ).
High expression of CDK5 indicates a good prognosis in nonmetastatic colon cancer, while it is the opposite in metastatic colon cancer, and the expression of CDK5 is unrelated to TILs. Patients with TIL-H have a better prognosis, with a proper cut-off value of 20% for colon cancer.
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