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一项泛癌分析表明,长链非编码 RNA HAND2-AS1 可作为包括结直肠腺癌在内的多种癌症的潜在预后、免疫调节和治疗生物标志物

英文原题:A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma.

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A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma.

PubMed 2023/12/02(内容时间) Cancer Cell Int Q1 · IF 7(JCR 2025)

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中文摘要

HAND2-AS1(HAND2 反义 RNA 1)长链非编码 RNA(lncRNA)已成为多种癌症类型起始的参与者,突显了其在肿瘤学过程和免疫反应中的关键作用。为了更深入地了解 HAND2-AS1 的功能细微差别并确定癌症免疫治疗的新途径,对该基因进行了全面评估。

在此,基于共表达网络分析和相互作用的 lncRNA-mRNA 基因构建,我们介绍了 HAND2-AS1 lncRNA,强调其在肿瘤发生和免疫调节中的关键作用。

我们的研究跨越 33 种不同的癌症类型,揭示了 HAND2-AS1 的异常表达模式、甲基化变异、突变特征和免疫参与。在大多数肿瘤中,HAND2-AS1 表现出下调倾向,显著与不良生存结果相关。功能富集分析的结果强烈表明 HAND2-AS1 参与肿瘤进展,并与不同肿瘤分类中的各种免疫途径相关。

此外,HAND2-AS1 表达与关键免疫细胞的浸润水平之间出现了正相关,不仅包括免疫抑制实体如肿瘤相关巨噬细胞、癌症相关成纤维细胞和 Tregs,还包括免疫效应细胞如 NK 细胞和 CD8+ T 细胞,跨越泛癌背景。

此外,HAND2-AS1 的差异表达似乎对各种途径有下游影响,因此暗示其作为不同癌症类型中的潜在调节因子。最后,我们使用 CRC 肿瘤和正常样本对 HAND2-AS1 进行了临床验证。

我们的研究揭示了HAND2-AS1作为泛癌肿瘤抑制因子的潜力,及其在肿瘤发生和免疫监视中的关键作用。HAND2-AS1表达增加有望成为预后评估、治疗策略的候选标志物,以及免疫治疗干预的焦点。

展开英文摘要原文

The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken.

Here, based on the co-expression network analysis and construction of interacting lncRNA-mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation.

Our study spans across 33 distinct cancer types, revealing the HAND2-AS1's aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1's engagement in tumor progression and its association with various immune pathways across diverse tumor classifications.

Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context.

Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types.

Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1.

Our study unveils HAND2-AS1's potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions.

论文信息

作者
Samadi P、Shahnazari M、Shekari A、Maghool F、Jalali A
第一作者单位
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.Iran
通讯作者单位
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. akram.jalali59@gmail.com.Iran
期刊
Cancer cell international2023 Dec 2
原文标识
PubMed 38042769 · DOI 10.1186/s12935-023-03163-7