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CYFIP2：潜在的胰腺癌生物标志物和免疫治疗靶点。

CYFIP2: potential pancreatic cancer biomarker and immunotherapeutic target.

作者信息

Xiao Cong, Zhang Xiaojuan, Hou Bobo, Wan Ping, Cao Zhenjun, Rao Xuefeng

机构信息

Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.

The First Affiliated Hospital of Nanchang University, Nanchang University, 17 Yongwai Zhengjie, Donghu District, Nanchang, 330006, People's Republic of China.

出版信息

Discov Oncol. 2024 Dec 30;15(1):847. doi: 10.1007/s12672-024-01650-5.

DOI:10.1007/s12672-024-01650-5
PMID:39739214
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11685368/
Abstract

OBJECTIVE

It has been shown that the CYFIP2 (Cytoplasmic FMR1-interacting protein 2) gene is apoptosis p53-dependent and is associated with poor prognosis in malignant tumors such as gastric cancer and other and cervical cancer. However, the prognostic potential of CYFIP2 in pancreatic cancer remains unclear. In this work, we first explain the great potential of CYFIP2 malignant progression from a broader perspective (pan-cancer) and confirm its oncogenic value in pancreatic cancer.

METHODS

The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, CELL and GEO databases were utilized to explore the distribution of the CYFIP2 gene in human cancers. Data were analyzed using a variety of web-based platforms and software such as R (4.3.2), UCSC, MethSurv, Cytoscape (v3.10.2), UALAND, STRING, TISIDB, Harmonizome 3.0, TIMER 2.0, TCIA and TIDE. The R packages R packages ?limma? and ?ggplot2? were used to compare and visualize CYFIP2 mRNA expression. The R packages ?survminer? and ?survival? were used to statistically analyze the relationship between CYFIP2 expression and the survival and prognosis of tumor patients. the R package ?ss GSEA? was used to assess the correlation between CYFIP2 expression and immune infiltration. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Variation Analysis (GSVA) were used to explore the multiple biological functions and regulatory pathways in which CYFIP2 co-expressed genes co-engage in pancreatic cancer. The R package ?maftool? was used to explore somatic mutation information in pancreatic cancer, and the TIDE database and the R package ?oncoPredic? were used to explore immunotherapeutic responses and sensitive drugs. Pancreatic cancer cell lines were constructed with the specific expression of CYFIP2 mRNA, and their invasive and metastatic abilities were analysed using scratch and transwell assays.

RESULTS

Bioinformatics analysis and in vitro experiments confirmed that CYFIP2 was differentially expressed in a variety of tumors and correlated with clinical stage, and could be used as a potential marker for evaluating the prognosis and immunotherapy of a variety of tumors, including KIRC (Kidney renal clear cell carcinoma), PAAD (Pancreatic adenocarcinoma), PAAD (Pancreatic adenocarcinoma), SKCM (Skin Cutaneous Melanoma), and UCEC (Uterine Corpus Endometrial Carcinoma).Mutations in the CYFIP2 gene and methylation indices can affect the prognosis of tumor patients. In addition, we found that CYFIP2 expression values in pancreatic cancer were positively correlated with the expression of most immune cells, especially CD8?+?T Cells, and significantly negatively correlated with macrophages M0, and negatively correlated with the metastatic and invasive ability of pancreatic cancer cells, which may provide new strategies and ideas for pancreatic cancer immunotherapy.

摘要

目的

已有研究表明，CYFIP2（细胞质FMR1相互作用蛋白2）基因是p53依赖性凋亡基因，与胃癌和其他恶性肿瘤如宫颈癌的不良预后相关。然而，CYFIP2在胰腺癌中的预后潜力仍不清楚。在本研究中，我们首先从更广泛的视角（泛癌）解释CYFIP2在恶性进展中的巨大潜力，并证实其在胰腺癌中的致癌价值。

方法

利用癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）数据库、CELL和GEO数据库，探索CYFIP2基因在人类癌症中的分布。使用多种基于网络的平台和软件，如R（4.3.2）、UCSC、MethSurv、Cytoscape（v3.10.2）、UALAND、STRING、TISIDB、Harmonizome 3.0、TIMER 2.0、TCIA和TIDE对数据进行分析。使用R包“limma”和“ggplot2”比较和可视化CYFIP2 mRNA表达。使用R包“survminer”和“survival”对CYFIP2表达与肿瘤患者生存和预后的关系进行统计分析。使用R包“ss GSEA”评估CYFIP2表达与免疫浸润的相关性。利用基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集变异分析（GSVA）探索CYFIP2共表达基因在胰腺癌中共同参与的多种生物学功能和调控途径。使用R包“maftool”探索胰腺癌中的体细胞突变信息，使用TIDE数据库和R包“oncoPredic”探索免疫治疗反应和敏感药物。构建CYFIP2 mRNA特异性表达的胰腺癌细胞系，采用划痕实验和Transwell实验分析其侵袭和转移能力。

结果

生物信息学分析和体外实验证实，CYFIP2在多种肿瘤中差异表达，与临床分期相关，可作为评估包括肾透明细胞癌（KIRC）、胰腺腺癌（PAAD）、皮肤黑色素瘤（SKCM）和子宫内膜癌（UCEC）等多种肿瘤预后和免疫治疗的潜在标志物。CYFIP2基因的突变和甲基化指数可影响肿瘤患者的预后。此外，我们发现胰腺癌中CYFIP2表达值与大多数免疫细胞的表达呈正相关，尤其是CD8 + T细胞，与M0巨噬细胞呈显著负相关，与胰腺癌细胞的转移和侵袭能力呈负相关，这可能为胰腺癌免疫治疗提供新的策略和思路。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88de/11685368/7517f8c856b6/12672_2024_1650_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88de/11685368/303a5711e192/12672_2024_1650_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88de/11685368/bec58191a28e/12672_2024_1650_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88de/11685368/eca31dd4183d/12672_2024_1650_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88de/11685368/5726b6008192/12672_2024_1650_Fig10_HTML.jpg
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