研究动态
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同型细胞内结构作为非小细胞肺癌的新型预后预测因子,通常位于侵袭前沿。

Homotypic cell-in-cell structure as a novel prognostic predictor in non-small cell lung cancer and frequently localized at the invasive front.

发表日期:2024 Aug 15
作者: Xiaona Liu, Rui Guo, Dongxuan Li, Ya'nan Wang, Jingya Ning, Shuanying Yang, Jun Yang
来源: Disease Models & Mechanisms

摘要:

同型细胞内结构(hoCIC)与肿瘤增殖、侵袭和转移相关,被认为是多种癌症的有前景的预后标志物。然而,hoCIC 在非小细胞肺癌 (NSCLC) 中的作用仍不清楚。肿瘤组织切片取自 411 名 NSCLC 患者。我们分析了临床病理学变量与 HOCIC 数量之间的关系。采用 LASSO 和多变量 Cox 回归分析来确定 NSCLC 的预后因素。使用 Kaplan-Meier 曲线和对数秩检验评估 hoCIC 对总生存期 (OS) 和无病生存期 (DFS) 的影响。使用 C 指数、时间相关曲线下面积 (AUC)、净重分类改进 (NRI)、综合辨别改进 (IDI)、校准曲线和决策曲线分析 (DCA) 开发和验证 OS 和 DFS 的预后模型。在队列中,56% 的患者患有 HOCIC,而 44% 的患者没有。值得注意的是,hoCIC 主要发现于肿瘤侵袭前沿。男性、吸烟、鳞状细胞癌、低分化、肿瘤大小 ≥ 3 cm、TNM分期晚期、淋巴结转移、胸膜侵犯、血管侵犯、坏死、P53突变、Ki-67高表达被确定为相对危险因素对于 HOCIC。此外,hoCIC 被发现是 OS 和 DFS 的重要预后因素,hoCIC 频率越高,预后越差。我们基于 hoCIC 构建了用于预测 1 年、3 年和 5 年 OS 和 DFS 的列线图,校准曲线显示预测结果与实际结果之间具有良好的一致性。 C指数、时间依赖性AUC、NRI、IDI和DCA分析的结果表明,将hoCIC纳入预后模型显着增强了其预测能力和临床适用性。 HoCIC 表明 NSCLC 患者的 OS 和 DFS 具有独立的预测价值。此外,hoCIC 在肿瘤侵袭前沿的频繁定位表明 hoCIC 与肿瘤侵袭和转移之间存在很强的关联。© 2024。作者。
Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan-Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.© 2024. The Author(s).