癌症干细胞标记物 CD44/SOX2 在食管鳞状细胞癌 (ESCC) 患者中的临床病理学意义以及构建预测总体生存率的列线图。
Clinicopathological significance of cancer stem cell marker CD44/SOX2 in esophageal squamous cell carcinoma (ESCC) patients and construction of a nomogram to predict overall survival.
发表日期:2024 Jun 30
作者:
Siyue Tian, Ruibin Ma, Yingmin Liu, Fei Chen, Xiaotong Huang, Qianqian Yang, Wei Nian, Zhiqin Fan
来源:
Stem Cell Research & Therapy
摘要:
食管鳞状细胞癌(ESCC)是上消化道系统常见的恶性肿瘤,其特点是预后不良、缺乏预后预测和高危病例识别的特异性指标。在我们的研究中,我们检查了 ESCC 中癌症干细胞 (CSC) 和标记物 CD44/SOX2 的表达水平,仔细检查了它们与临床病理学参数的关联,并开发了预测列线图模型。该模型结合了CD44/SOX2,旨在预测食管鳞癌患者的总生存期(OS)。采用免疫组化方法检测68例食管鳞癌患者癌组织和癌旁组织中CD44和SOX2的表达水平。随后分析CD44/SOX2表达与临床病理参数之间的相关性。通过单变量和多变量 Cox 回归分析评估影响 ESCC 患者预后的因素。利用这些多元回归分析的结果,建立了列线图预后模型,以提供 ESCC 患者生存结果的个体化预测。使用一致性指数(C-index)和校准曲线评估列线图预后模型的预测准确性。ESCC患者肿瘤组织中CD44的表达水平显着升高。同样,SOX2在ESCC患者的肿瘤组织中显着过表达。 ESCC中SOX2的阳性表达与病理T期和癌胚抗原的存在有很强的相关性。 CD44和SOX2共阳性表达与病理T分期和肿瘤淋巴结转移(TNM)分期显着相关。此外,肿瘤组织中表现出 CD44 阳性表达的 ESCC 患者通常预后更不良。与其他组合的患者相比,CD44 和 SOX2 的共表达导致患者预后更差。多变量Cox回归分析将CD44和SOX2的共表达、病理T分期和淋巴结转移确定为ESCC患者的独立预后指标。随后将这三个确定的变量纳入列线图中以预测 OS。测量模型的C指数和受试者工作特征曲线下面积显示出良好的个体预测能力。该预后模型将患者分为低风险和高风险类别。分析显示,与高风险组相比,低风险组的 5 年 OS 率显着较高。CD44 水平升高表明存在 CSC,与 ESCC 的肿瘤发生密切相关,并且强烈预测患者的不利情况结果。同时,SOX2 基因在 ESCC 中表达升高,显着加速肿瘤进展并促进更广泛的疾病浸润。 CD44 和 SOX2 的共表达与 ESCC 患者的预后显着相关,可作为可靠、独立的预后标志物。我们构建的列线图结合了 CD44/SOX2 表达,增强了 OS 预测并促进 ESCC 患者的风险分层。2024 转化癌症研究。版权所有。
Esophageal squamous cell carcinoma (ESCC), a prevalent malignancy within the upper gastrointestinal system, is characterized by its unfavorable prognosis and the absence of specific indicators for outcome prediction and high-risk case identification. In our research, we examined the expression levels of cancer stem cells (CSCs), markers CD44/SOX2 in ESCC, scrutinized their association with clinicopathological parameters, and developed a predictive nomogram model. This model, which incorporates CD44/SOX2, aims to forecast the overall survival (OS) of patients afflicted with ESCC.Immunohistochemistry was utilized to detect the expression levels of CD44 and SOX2 in both cancerous and paracancerous tissues of 68 patients with ESCC. The correlation between CD44/SOX2 expression and clinicopathological parameters was subsequently analyzed. Factors impacting the prognosis of ESCC patients were assessed through univariate and multivariate Cox regression analyses. Leveraging the results of these multivariate regression analyses, a nomogram prognostic model was established to provide individualized predictions of ESCC patient survival outcomes. The predictive accuracy of the nomogram prognostic model was evaluated using the consistency index (C-index) and calibration curves.The expression levels of CD44 were markedly elevated in the tumor tissues of ESCC patients. Similarly, SOX2 was significantly overexpressed in the tumor tissues of ESCC patients. The positive expression of SOX2 in ESCC demonstrated a strong correlation with both the pathological T-stage and the presence of carcinoembryonic antigen. CD44 and SOX2 co-positive expression was significantly associated with the pathological T-stage and tumor node metastasis (TNM) stage. Furthermore, ESCC patients exhibiting CD44-positive expression in their tumor tissue generally had a more adverse prognosis. The co-expression of CD44 and SOX2 resulted in a grimmer prognosis compared to patients with other combinations. Multivariate Cox regression analysis identified the co-expression of CD44 and SOX2, the pathological T-stage, and lymph node metastasis as independent prognostic indicators for ESCC patients. The three identified variables were subsequently incorporated into a nomogram for predicting OS. The C-index of the measurement model and the area under the curve of the subjects' work characteristics showed good individual prediction. This prognostic model stratified patients into low- and high-risk categories. Analysis revealed that the 5-year OS rate was significantly higher in the low-risk group compared to the high-risk group.Elevated CD44 levels, indicative of CSC presence, are intimately linked with the oncogenesis of ESCC and are strongly predictive of unfavorable patient outcomes. Concurrently, the SOX2 gene exhibits a heightened expression in ESCC, markedly accelerating tumor progression and fostering more extensive disease infiltration. The co-expression of CD44 and SOX2 correlates significantly with ESCC patient prognosis, serving as a reliable, independent prognostic marker. Our constructed nomogram, incorporating CD44/SOX2 expression, enhances the prediction of OS and facilitates risk stratification in ESCC patients.2024 Translational Cancer Research. All rights reserved.