Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.
Center of Tumor Immunology and Cytotherapy, Medical Research Center of the Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Curr Gene Ther. 2022;22(5):449-461. doi: 10.2174/1566523222666220613113647.
Heterogeneous nuclear ribonucleoproteins (hnRNPs), a large family of RNAbinding proteins, have been implicated in tumor progression in multiple cancer types. However, the expression pattern and prognostic value of hnRNPs in five gastrointestinal (GI) cancers, including gastric, colorectal, esophageal, liver, and pancreatic cancer, remain to be investigated.
The current research aimed to identify prognostic biomarkers of the hnRNP family in five major types of gastrointestinal cancer.
Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier Plotter were used to explore the hnRNPs expression levels concerning clinicopathological parameters and prognostic values. The protein level of hnRNPU was validated by immunohistochemistry (IHC) in human tissue specimens. Genetic alterations of hnRNPs were analyzed using cBioportal, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to illustrate the biological functions of co-expressed genes of hnRNPs.
The vast majority of hnRNPs were highly expressed in five types of GI cancer tissues compared to their adjacent normal tissues, and mRNA levels of hnRNPA2B1, D, Q, R, and U were significantly different in various GI cancer types at different stages. In addition, Kaplan-Meier analysis revealed that the increased hnRNPs expression levels were correlated with better prognosis in gastric and rectal cancer patients (log-rank p < 0.05). In contrast, patients with high levels of hnRNPs exhibited a worse prognosis in esophageal and liver cancer (log-rank p < 0.05). Using immunohistochemistry, we further confirmed that hnRNPU was overexpressed in gastric, rectal, and liver cancers. In addition, hnRNPs genes were altered in patients with GI cancers, and RNA-related processing was correlated with hnRNPs alterations.
We identified differentially expressed genes of hnRNPs in tumor tissues versus adjacent normal tissues, which might contribute to predicting tumor types, early diagnosis, and targeted therapies in five major types of GI cancer.
异质性核核糖核蛋白（hnRNPs）是一个庞大的 RNA 结合蛋白家族，其在多种癌症类型中与肿瘤进展有关。然而，hnRNPs 在包括胃癌、结直肠癌、食管癌、肝癌和胰腺癌在内的五种胃肠道（GI）癌症中的表达模式和预后价值仍有待研究。
本研究旨在确定 hnRNP 家族在五种主要胃肠道癌症中的预后生物标志物。
使用 Oncomine、基因表达谱分析交互式分析（GEPIA）和 Kaplan-Meier Plotter 来探讨 hnRNPs 表达水平与临床病理参数和预后价值的关系。hnRNPU 的蛋白水平通过免疫组织化学（IHC）在人类组织标本中进行验证。使用 cBioportal 分析 hnRNPs 的遗传改变，并进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析以说明 hnRNPs 共表达基因的生物学功能。
与相应的邻近正常组织相比，绝大多数 hnRNPs 在五种 GI 癌组织中高表达，并且在不同阶段的不同 GI 癌类型中，hnRNPA2B1、D、Q、R 和 U 的 mRNA 水平存在显著差异。此外，Kaplan-Meier 分析表明，hnRNPs 表达水平的增加与胃癌和直肠癌患者的更好预后相关（对数秩检验 p<0.05）。相比之下，食管和肝癌患者中高水平的 hnRNPs 预示着更差的预后（对数秩检验 p<0.05）。通过免疫组织化学，我们进一步证实 hnRNPU 在胃癌、直肠癌和肝癌中过表达。此外，GI 癌症患者的 hnRNPs 基因发生改变，并且 RNA 相关加工与 hnRNPs 改变相关。
我们鉴定了肿瘤组织与邻近正常组织中 hnRNPs 的差异表达基因，这可能有助于预测五种主要类型的 GI 癌症的肿瘤类型、早期诊断和靶向治疗。
