收稿日期: 2025-06-18
网络出版日期: 2025-10-10
基金资助
国家自然科学基金项目(81660416);国家自然科学基金项目(82260468);广西自然科学基金项目(2023GXNSFAA026341);广西自然科学基金项目(2023GXNSFAA026143);广西适宜技术推广项目(S2024006)
The expression of PCBP1 in gastric cancer and its relationship with ferroptosis factor STUB1
Received date: 2025-06-18
Online published: 2025-10-10
目的 旨在通过生物信息学分析结合实验验证,探讨PCBP1(Poly(rC)-Binding Protein 1)在胃癌组织中的表达特征及其临床意义,对其与铁死亡主要调控因子STUB1(STIP1 Homology and U-Box Containing Protein 1)的关系研究。并通过免疫组化实验验证PCBP1与STUB1在胃癌中的表达模式及其与临床病理特征的关系。为新型胃癌靶向治疗策略提供重要的理论支撑和潜在的干预靶点。 方法 从TIMER 2.0在线分析网站中获取PCBP1在胃癌及癌旁组织的基因表达数据。利用癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库中胃癌数据(STAD)进行KEGG通路富集分析,并揭示其潜在作用机制;在铁死亡调控通路中找出主要调控因子STUB1。随后,采用免疫组化法检测33例胃癌组织及对应癌旁组织中PCBP1和STUB1的表达情况。将所收集的病例依据不同的分化程度、年龄、性别、肿瘤浸润深度、TNM分期及病理学形态进行分组,观察二者的阳性表达率,采用χ2检验分析两者之间及其与临床和病理特征间的相关性,进一步探讨PCBP1和STUB1与胃癌恶性程度的关系。 结果 免疫组化结果显示PCBP1在癌组织中的阳性表达率为69.7%,明显高于癌旁组织中的阳性表达率48.5%;STUB1在癌组织中的阳性表达率为39.4%,低于癌旁组织中的阳性表达率54.5%,两者差异均有统计学意义(P < 0.05)。PCBP1的阳性表达率与肿瘤分化程度、淋巴结转移及Lauren分型有相关性(P < 0.05); 与患者的年龄、性别、浸润深度、临床分期、神经浸润、脉管侵犯无相关性(P > 0.05)。STUB1的阳性表达率与肿瘤分化程度、浸润深度、淋巴结转移及 Lauren分型有相关性(P < 0.05),但与患者的年龄、性别、临床分期、神经浸润、脉管侵犯无相关性(P > 0.05)。PCBP1(癌)与STUB1(癌)的Spearman相关系数为-0.413,P为0.017,表明两者之间存在显著的负相关性。 结论 PCBP1可通过调控铁死亡通路中主要调控因子STUB1参与胃癌的恶性进展。为胃癌的分子机制探索及潜在治疗靶点提供了新的理论依据。
卢旭满 , 史正一 , 雷元睿 , 黄海滨 , 邓仁淼 , 董旭东 , 黄宇亮 , 孔凡彪 , 王晓通 . PCBP1在胃癌中的表达及其与铁死亡因子STUB1的关系[J]. 实用医学杂志, 2025 , 41(19) : 3026 -3033 . DOI: 10.3969/j.issn.1006-5725.2025.19.010
Objective To investigate the expression characteristics of poly (rC)-binding protein 1 (PCBP1) in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification, and to identify its relationship with STIP1 homology and U-Box containing protein 1 (STUB1). Specifically, this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer. Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website. KEGG pathway enrichment analysis was performed using gastric cancer data (STAD) in the TCGA (the Cancer Genome Atlas) database, and its potential mechanism was determined. The main regulatory factor STUB1 was found in the ferroptosis regulatory pathway. Subsequently, PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry. The collected cases were grouped according to different degrees of differentiation, age, gender, tumor size, depth of tumor invasion, TNM stage and pathological morphology. The positive expression rates of PCBP1 and STUB1 were observed. The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test. Finally, the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored. Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7 %, which was significantly higher than that in adjacent tissues (48.5%). The positive expression rate of STUB1 in cancer tissues was 39.4 %, which was lower than that in adjacent tissues (54.5 %), statistically significant difference (P < 0.05). The positive expression rate of PCBP1 was correlated with tumor differentiation, lymph node metastasis and Lauren classification (P < 0.05), but not with patient's age, gender, depth of invasion, clinical stage, nerve infiltration, and intravascular tumor thrombus (P > 0.05). The positive expression rate of STUB1 was correlated with tumor differentiation, depth of invasion, lymph node metastasis and Lauren classification (P < 0.05). The Spearman correlation coefficient between PCBP1 (cancer) and STUB1 (cancer) was -0.413, with P = 0.017 (P < 0.05), indicating that there was a significant negative correlation between them. Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway. Theoretically, it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.
Key words: gastric cancer; PCBP1; STUB1; bioinformatics; iron death; immunohistochemistry
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