介绍：尽管Krüpple-like因子4（KLF4）在HCC肿瘤发生中作为肿瘤抑制因子的分子机制已经得到彻底研究，但是在HCC患者中其精确预后和对肿瘤免疫微环境的影响方面的临床应用还需要进一步研究。方法：生物信息学和免疫组化（IHC）被用于验证组织芯片（TMA）中含有HCC样本的KLF4表达。使用Cox回归模型，鉴定独立的预后因素并应用于制定诊断模型。决策曲线分析（DCA）证明模型的优越性。应用GO和KEGG通路分析对KLF4进行功能研究。GSVA程序探索KLF4表达与肿瘤浸润免疫细胞之间的联系，而CAMOIP则用于构建KLF4表达的免疫评分。研究与KLF4表达有关的免疫相关基因标志物的变化。IHC在TMA中验证了免疫细胞浸润和KLF4表达之间的关联。结果：报道了HCC具有明显的KLF4消耗。KLF4的缺失与HCC的进展临床病理特征有关，预示着患者的不良预后。使用KLF4表达、肿瘤分化和TNM分期制定的诊断模型，比仅使用TNM分期更准确地评估HCC患者的预后。KLF4表达与免疫相关功能、巨噬细胞、CD8+T细胞和其他免疫细胞的浸润以及免疫检查点的升高有关。在HCC TMA中，CD8+T细胞和巨噬细胞浸润水平的升高与KLF4表达升高相关。结论：HCC中的KLF4丧失是影响肿瘤免疫微环境（TIME）的预后生物标志物。Copyright © 2023 Chen, Zhu, Li, Fan, Lou, Zhang, Huang and Sun.

Introduction: Although the molecular mechanisms of Krüpple-like factor 4 (KLF4) as a tumor suppressor in HCC tumorigenesis have been thoroughly examined, its clinical application in terms of precise prognostication and its influence on tumor immune microenvironment in patients with HCC require further investigation. Methods: Bioinformatics and immunohistochemistry (IHC) were used to validate KLF4 expressions in a tissue microarray (TMA) containing HCC samples. Using Cox regression models, independent prognostic factors were identified and employed in the development of nomograms. Decision curve analysis (DCA) demonstrated the superiority of the nomograms. GO and KEGG pathway analyses were applied to the functional study of KLF4. The GSVA program explored the link between KLF4 expression and tumor-infiltrating immune cells, and CAMOIP was used to construct KLF4 expression immune scores. Changes in immune-related gene markers were also investigated in relation to KLF4 expression. The association between immune cell infiltration and KLF4 expression was validated by IHC in TMA. Results: HCC was reported to have a notable depletion of KLF4. The absence of KLF4 was associated with advanced clinicopathological characteristics of HCC and predicted a bad prognosis for patients. Nomograms constructed using KLF4 expression, tumor differentiation, and TNM stage provided a more accurate prognostic assessment of HCC patients than TNM stage alone. KLF4 expression was associated with immunological-related functions, infiltration of macrophages, CD8+ T cells, and other immune cells, and elevation of immune checkpoints. Higher levels of CD8+ T cells and macrophage infiltration are associated with increased KLF4 expression in HCC TMA. Conclusion: KLF4 loss in HCC is a prognostic biomarker that influences the tumor immune microenvironment (TIME).Copyright © 2023 Chen, Zhu, Li, Fan, Lou, Zhang, Huang and Sun.