Cancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, China.
School of Basic Medicine Sciences, Henan University of Chinese Medicine; Zhengzhou 450004, China.
Genes (Basel). 2022 Oct 3;13(10):1786. doi: 10.3390/genes13101786.
Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan-Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples.
The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = -0.317, -value 3.111 × 10), miR-33b-5p (R= -0.238, -value 1.166 × 10), and miR-582-3p (R = -0.214, -value 8.430 × 10), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer.
MAP4K4 might be closely related to gastric cancer's progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.
胃癌仍然是全球最普遍和致死率最高的疾病。MAP4K4 是 Ste20 家族的一个成员，在多种病理学中发挥重要作用，包括癌症。然而，其在胃癌中的作用尚未完全阐明。因此，本研究旨在确定 MAP4K4 在胃癌中的促肿瘤作用，以及它是否可作为一种新的、可靠的生物标志物来预测胃癌的预后。为此，我们根据 MAP4K4 的表达水平将样本分为高表达组和低表达组。使用 Kaplan-Meier 生存分析评估 MAP4K4 表达与预后的关联。此外，还使用 ESTIMATE 进行免疫浸润分析，以评估样本的肿瘤免疫评分。
研究结果显示，肿瘤样本中 MAP4K4 的表达明显高于相邻样本。高表达组显著富集于肿瘤相关通路，如 PI3K-Akt 信号通路。此外，免疫浸润分析显示免疫评分与 MAP4K4 表达之间存在正相关。我们还观察到，miRNA 如 miR-192-3p（R = -0.317，-值 3.111×10）、miR-33b-5p（R = -0.238，-值 1.166×10）和 miR-582-3p（R = -0.214，-值 8.430×10）可能对 MAP4K4 具有负向调节作用。此外，我们鉴定了几个可能调节 MAP4K4 的转录因子、泛素化蛋白和相互作用蛋白。还确定了 MAP4K4 与 DNA 甲基化的关系。最后，我们验证了 MAP4K4 的高表达及其对促进癌症的影响。
MAP4K4 可能与胃癌的进展、侵袭和转移密切相关。其高表达对胃癌患者的预后产生负面影响。这表明 MAP4K4 可能是胃癌的一个重要预后因素，并可作为新的潜在预后检测和治疗靶点。
