DataSheet_1_Pan-cancer analysis of Krüppel-like factor 3 and its carcinogenesis in pancreatic cancer.docx

BackgroundKrüppel-like factor 3 (KLF3) is a key transcriptional repressor, which is involved in various biological functions such as lipogenesis, erythropoiesis, and B cell development, and has become one of the current research hotspots. However, the role of KLF3 in the pan-cancer and tumor microenvironment remains unclear.
MethodsTCGA and GTEx databases were used to evaluate the expression difference of KLF3 in pan-cancer and normal tissues. The cBioPortal database and the GSCALite platform analyzed the genetic variation and methylation modification of KLF3. The prognostic role of KLF3 in pan-cancer was identified using Cox regression and Kaplan-Meier analysis. Correlation analysis was used to explore the relationship between KLF3 expression and tumor mutation burden, microsatellite instability, and immune-related genes. The relationship between KLF3 expression and tumor immune microenvironment was calculated by ESTIMATE, EPIC, and MCPCOUNTER algorithms. TISCH and CancerSEA databases analyzed the expression distribution and function of KLF3 in the tumor microenvironment. TIDE, GDSC, and CTRP databases evaluated KLF3-predicted immunotherapy response and sensitivity to small molecule drugs. Finally, we analyzed the role of KLF3 in pancreatic cancer by in vivo and in vitro experiments.
ResultsKLF3 was abnormally expressed in a variety of tumors, which could effectively predict the prognosis of patients, and it was most obvious in pancreatic cancer. Further experiments verified that silencing KLF3 expression inhibited pancreatic cancer progression. Functional analysis and gene set enrichment analysis found that KLF3 was involved in various immune-related pathways and tumor progression-related pathways. In addition, based on single-cell sequencing analysis, it was found that KLF3 was mainly expressed in CD4Tconv, CD8T, monocytes/macrophages, endothelial cells, and malignant cells in most of the tumor microenvironment. Finally, we assessed the value of KLF3 in predicting response to immunotherapy and predicted a series of sensitive drugs targeting KLF3.
ConclusionThe role of KLF3 in the tumor microenvironment of various types of tumors cannot be underestimated, and it has significant potential as a biomarker for predicting the response to immunotherapy. In particular, it plays an important role in the progression of pancreatic cancer.

背景：Krüppel样因子3（Krüppel-like factor 3, KLF3）是一类关键的转录抑制因子，参与脂肪生成、红细胞生成以及B细胞发育等多种生物学过程，是当前的研究热点之一。然而，KLF3在泛癌及肿瘤微环境中的作用仍不明确。
方法：本研究采用癌症基因组图谱（The Cancer Genome Atlas, TCGA）与基因型-组织表达数据库（Genotype-Tissue Expression, GTEx）评估KLF3在泛癌组织与正常组织中的表达差异；借助cBioPortal数据库与GSCALite平台分析KLF3的遗传变异与甲基化修饰；通过Cox回归与Kaplan-Meier分析明确KLF3在泛癌中的预后价值；利用相关性分析探究KLF3表达与肿瘤突变负荷、微卫星不稳定性及免疫相关基因的关联；通过ESTIMATE、EPIC与MCPCOUNTER算法计算KLF3表达与肿瘤免疫微环境的相关性；运用TISCH与CancerSEA数据库分析KLF3在肿瘤微环境中的表达分布与功能；通过TIDE、GDSC与CTRP数据库评估KLF3预测免疫治疗响应及小分子药物敏感性的效能；最后通过体内外实验分析KLF3在胰腺癌中的作用。
结果：KLF3在多种肿瘤中存在异常表达，可有效预测患者预后，且该预测效能在胰腺癌中最为显著。后续实验验证了沉默KLF3的表达可抑制胰腺癌的进展。功能分析与基因集富集分析发现，KLF3参与多种免疫相关通路及肿瘤进展相关通路。此外，基于单细胞测序分析，本研究发现多数肿瘤微环境中KLF3主要表达于CD4Tconv细胞、CD8+T细胞、单核细胞/巨噬细胞、内皮细胞及恶性肿瘤细胞中。最后，本研究评估了KLF3在预测免疫治疗响应中的价值，并筛选出一系列针对KLF3的敏感药物。
结论：KLF3在多种肿瘤的肿瘤微环境中的作用不容忽视，其作为预测免疫治疗响应的生物标志物具有显著潜力，尤其在胰腺癌的进展过程中发挥重要作用。