Chen Desheng, Zhu Qi, Li Tiewen, Fan Xuhui, Lou Yichao, Zhang Yi, Huang Kejie, Sun Hongcheng
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institution for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Genet. 2023 Mar 2;14:1106952. doi: 10.3389/fgene.2023.1106952. eCollection 2023.
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. : 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. : 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. : KLF4 loss in HCC is a prognostic biomarker that influences the tumor immune microenvironment (TIME).
尽管Krüpple样因子4（KLF4）作为肝癌发生过程中的肿瘤抑制因子的分子机制已得到充分研究，但其在精确预后方面的临床应用及其对肝癌患者肿瘤免疫微环境的影响仍需进一步研究。使用生物信息学和免疫组织化学（IHC）方法在包含肝癌样本的组织微阵列（TMA）中验证KLF4的表达。利用Cox回归模型确定独立预后因素并用于构建列线图。决策曲线分析（DCA）证明了列线图的优越性。GO和KEGG通路分析应用于KLF4的功能研究。GSVA程序探索KLF4表达与肿瘤浸润免疫细胞之间的联系，并且使用CAMOIP构建KLF4表达免疫评分。还研究了与KLF4表达相关的免疫相关基因标志物的变化。通过TMA中的IHC验证免疫细胞浸润与KLF4表达之间的关联。据报道，肝癌中KLF4明显缺失。KLF4的缺失与肝癌的晚期临床病理特征相关，并预测患者预后不良。使用KLF4表达、肿瘤分化和TNM分期构建的列线图比单独的TNM分期能为肝癌患者提供更准确的预后评估。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。肝癌TMA中较高水平的CD8 T细胞和巨噬细胞浸润与KLF4表达增加相关。肝癌中KLF4缺失是一种影响肿瘤免疫微环境（TIME）的预后生物标志物。
