GUCA2A dysregulation as a promising biomarker for accurate diagnosis and prognosis of colorectal cancer.

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Experimental Medicine Pub Date : 2024-11-01 DOI:10.1007/s10238-024-01512-y
Pooya Jalali, Shahram Aliyari, Marziyeh Etesami, Mahsa Saeedi Niasar, Sahar Taher, Kaveh Kavousi, Ehsan Nazemalhosseini Mojarad, Zahra Salehi
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Abstract

Colorectal cancer is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. We performed analysis of colorectal cancer microarray and the TCGA colon adenoma carcinoma (COAD) datasets to identify DEGs associated with COAD and common DEGs were selected. Furthermore, a pan-cancer analysis encompassing 33 different cancer types was performed to identify differential genes significantly expressed only in COAD. Then, comprehensively in-silico analysis including gene set enrichment analysis, constructing Protein-Protein interaction, co-expression, and competing endogenous RNA (ceRNA) networks, investigating the correlation between tumor-immune signatures in distinct tumor microenvironment and also the potential interactions between the identified gene and various drugs was executed. Further, the candidate gene was experimentally validated in tumoral colorectal tissues and colorectal adenomatous polyps by qRael-Time PCR. GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC|> 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with a 99.6% and 78% area under the curve (AUC) based on TCGA-COAD and colon cancer patients. In addition, GUCA2A expression in adenomatous polyps equal to or larger than 5 mm was significantly lower compared to smaller than 5 mm. Moreover, low expression of GUCA2A significantly impacted overall patient survival. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. The ceRNA constructed included GUCA2A, 8 shared miRNAs, and 61 circRNAs. This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.

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GUCA2A 失调是准确诊断和预后结直肠癌的一种有前途的生物标记物。
结直肠癌是导致全球死亡的主要原因之一,也是提高预期寿命的一大障碍。这项研究的主要目的是找出与结直肠癌密切相关的独特差异表达基因(DEG)。通过实现这一目标,研究旨在为转化医学领域贡献有价值的见解。我们对结直肠癌微阵列和 TCGA 结肠腺瘤癌(COAD)数据集进行了分析,以确定与 COAD 相关的 DEGs,并筛选出常见的 DEGs。此外,还对 33 种不同癌症类型进行了泛癌症分析,以确定仅在 COAD 中显著表达的差异基因。然后,进行了包括基因组富集分析、构建蛋白-蛋白相互作用、共表达和竞争性内源性 RNA(ceRNA)网络在内的全面海内分析,研究了不同肿瘤微环境中肿瘤-免疫特征之间的相关性,以及所识别基因与各种药物之间的潜在相互作用。此外,还通过 qRael-Time PCR 在肿瘤结直肠组织和结直肠腺瘤息肉中对候选基因进行了实验验证。GUCA2A 成为结直肠癌特异性的重要 DEG(|log2FC|> 1,调整后的 q-value
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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