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Abstract：
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.
摘要：
同源细胞在细胞结构（hoCIC）与肿瘤增殖有关，入侵,和转移，被认为是各种癌症的有希望的预后标志物。然而,hoCIC在非小细胞肺癌(NSCLC)中的作用尚不清楚.肿瘤组织切片取自411名NSCLC患者。我们分析了临床病理变量与hoCIC数量之间的关系。采用LASSO和多变量Cox回归分析确定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索引开发并验证了OS和DFS的预后模型，时间依赖性曲线下面积（AUC），净重新分类改进(NRI)，综合歧视改进(IDI)，校准曲线和判定曲线分析(DCA)。在队列中，56％的患者有hoCIC，而44％的患者没有。值得注意的是,hoCIC主要发现于肿瘤浸润前沿。男性,吸烟,鳞状细胞癌,低分化,肿瘤大小≥3厘米，高级TNM阶段，淋巴结转移,胸膜侵犯,血管浸润,坏死,P53突变,和Ki-67的高表达被确定为hoCIC的相对危险因素。此外，HOCIC被发现是OS和DFS的重要预后因素，更高的HOCIC频率与较差的结果相关。我们构建了用于预测1-，3-,以及基于hoCIC的5年OS和DFS，校准曲线显示预测和实际结果之间的良好一致性。C指数的结果，时间依赖性AUC，NRI,IDI,和DCA分析表明，将hoCIC纳入预后模型可显着增强其预测能力和临床适用性。HoCIC显示了NSCLC患者OS和DFS的独立指示值。此外，hoCIC在肿瘤浸润前沿的频繁定位表明,hoCIC与肿瘤浸润和转移之间存在很强的相关性.
