Zou Junwei, Li Zhenhan, Xie Jiaheng, Wu Zhaoying, Huang Yujin, Xie Hao, Xu Huiqiu, Huang Yong, Zhou Hailang
Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
School of Clinical Medicine, Wannan Medical College, Wuhu, Anhui, China.
J Oncol. 2022 Aug 27;2022:9077424. doi: 10.1155/2022/9077424. eCollection 2022.
Colon cancer is a common malignant tumor in the digestive tract, with relatively high rates of morbidity and mortality. It is the third most common type of tumor in the world. The effective treatment of advanced colon cancer is limited, so it is particularly important to study the new pathogenesis of colon cancer. Ferroptosis is a nonapoptotic regulated cell death mode driven by iron-dependent lipid peroxidation, a process which has been discovered in recent years. Autophagy involves lysosomal degradation pathways that promote or prevent cell death. High levels of autophagy are associated with ferroptosis, but a clear association has not yet been made between ferroptosis and autophagy in colon cancer. Through the analysis of transcriptome expression profiling data in colon cancer, we obtained the common upregulated genes and downregulated genes by recording the intersection of the differentially expressed genes in each dataset. Solute Carrier Family 2 Member 1 (SLC2A1) was identified by combining autophagy genes obtained from GeneCards and ferroptosis genes obtained from FerrDb. In order to explore the clinical significance and prognostic value of SLC2A1, we utilized massive databases to conduct an in-depth exploration of the methylation of SLC2A1, and we also investigated the differences in immune infiltration between tumor and normal tissues. We found that there are abundant methylation sites in SLC2A1 and that the methylation of SLC2A1 is correlated with the immunosuppression of tumor tissue. We discovered that during the induction of environmental factors, the transcription and methylation levels of SLC2A1 were greatly increased, autophagy and ferroptosis were inhibited, and the immune system was defective, resulting in a poor prognosis for patients. These results suggest that the autophagy and ferroptosis-related gene SLC2A1 is involved in the tumor immune regulation of colon cancer, and SLC2A1 may become a new therapeutic target for colon cancer.
结肠癌是消化道常见的恶性肿瘤，发病率和死亡率相对较高。它是世界上第三大常见肿瘤类型。晚期结肠癌的有效治疗方法有限，因此研究结肠癌的新发病机制尤为重要。铁死亡是一种由铁依赖性脂质过氧化驱动的非凋亡性调节细胞死亡模式，这一过程是近年来发现的。自噬涉及促进或阻止细胞死亡的溶酶体降解途径。高水平的自噬与铁死亡相关，但结肠癌中铁死亡与自噬之间尚未建立明确的关联。通过对结肠癌转录组表达谱数据的分析，我们通过记录每个数据集中差异表达基因的交集，获得了共同上调基因和下调基因。通过结合从GeneCards获得的自噬基因和从FerrDb获得的铁死亡基因，鉴定出溶质载体家族2成员1（SLC2A1）。为了探讨SLC2A1的临床意义和预后价值，我们利用大量数据库对SLC2A1的甲基化进行了深入研究，并调查了肿瘤组织与正常组织之间免疫浸润的差异。我们发现SLC2A1中有丰富的甲基化位点，且SLC2A1的甲基化与肿瘤组织的免疫抑制相关。我们发现，在环境因素诱导过程中，SLC2A1的转录和甲基化水平大幅增加，自噬和铁死亡受到抑制，免疫系统存在缺陷，导致患者预后不良。这些结果表明，自噬和铁死亡相关基因SLC2A1参与结肠癌的肿瘤免疫调节，SLC2A1可能成为结肠癌的新治疗靶点。
