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长链非编码RNA在结直肠癌的临床意义、免疫格局及致癌过程中的作用。

The roles of lncRNA in clinical implications, immune landscape and carcinogenesis of colorectal cancer.

作者信息

Chen Tao, Jiang Qiusheng, Wang Zhenlin, Zhang Hongqiang, Fu Zan

机构信息

Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of General Surgery, Nanjing Pukou People's Hospital, Nanjing, China.

出版信息

Transl Cancer Res. 2024 Jul 31;13(7):3465-3481. doi: 10.21037/tcr-24-145. Epub 2024 Jul 19.

Abstract

BACKGROUND

Previously, long non-coding RNA (lncRNA) gene was reported to participate in the construction of an immune-related lncRNA signature, which showed promising clinical predictive value in colorectal cancer (CRC) patients. However, the clinical and immunological significance and biological function of in CRC remain unclear. In this study, we aim to explore the roles of in CRC progression, thereby opening an avenue for CRC treatment.

METHODS

Our study collected data from The Cancer Genome Atlas (TCGA) database and investigated the role of in CRC through bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods evaluated the immune infiltration. The biological functions of in CRC were validated by experiments. Gene set enrichment analysis (GSEA) was used to estimate the enrichment of functional pathways and gene signatures.

RESULTS

In this work, high expression of was found in CRC and was positively associated with tumor-node-metastasis (TNM) stage in CRC. expression had a strong relationship with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Additionally, expression was associated with StromalScore, ImmuneScore, ESTIMATEScore, immune cell infiltration (ICI) levels and immune checkpoint (ICP) genes expression in CRC. Subsequent results showed that immunotherapy could be more effective in CRC patients with low- expression using the immunophenoscore (IPS). We confirmed that the transcript of gene was highly expressed in CRC tissues and cell lines. experiments indicated that knockdown reduced the proliferation, migration and invasion of CRC cells. Finally, our GSEA results showed that the majority of the differentially enriched signaling pathways between the high- and low- expression groups were immune-related.

CONCLUSIONS

Taken together, our study demonstrates that lncRNA gene is associated with immunological characteristics in CRC and promotes malignant progression of CRC. Moreover, can be potentially used as an immunotherapeutic indicator and a therapeutic target for CRC patients.

摘要

背景

此前,有报道称长链非编码RNA(lncRNA)基因参与了免疫相关lncRNA特征的构建,这在结直肠癌(CRC)患者中显示出了有前景的临床预测价值。然而,其在CRC中的临床和免疫学意义以及生物学功能仍不清楚。在本研究中,我们旨在探索其在CRC进展中的作用,从而为CRC治疗开辟一条途径。

方法

我们的研究从癌症基因组图谱(TCGA)数据库收集数据,并通过生物信息学分析研究其在CRC中的作用。利用已知RNA转录本相对子集估计进行细胞类型鉴定(CIBERSORT)和使用表达数据估计恶性肿瘤组织中的基质和免疫细胞(ESTIMATE)方法评估免疫浸润情况。通过实验验证其在CRC中的生物学功能。基因集富集分析(GSEA)用于估计功能通路和基因特征的富集情况。

结果

在本研究中,发现其在CRC中高表达,且与CRC的肿瘤-淋巴结-转移(TNM)分期呈正相关。其表达与结肠腺癌(COAD)中的微卫星不稳定性(MSI)密切相关。此外,其表达与CRC中的基质评分、免疫评分、ESTIMATE评分、免疫细胞浸润(ICI)水平以及免疫检查点(ICP)基因表达相关。随后的结果表明,使用免疫表型评分(IPS),免疫疗法在低表达的CRC患者中可能更有效。我们证实该基因的转录本在CRC组织和细胞系中高表达。实验表明,敲低该基因可降低CRC细胞的增殖、迁移和侵袭能力。最后,我们的GSEA结果表明,高表达组和低表达组之间大多数差异富集的信号通路与免疫相关。

结论

综上所述,我们的研究表明lncRNA基因与CRC的免疫学特征相关,并促进CRC的恶性进展。此外,其有可能作为CRC患者的免疫治疗指标和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/445f/11319950/6d08e2d47c42/tcr-13-07-3465-f1.jpg

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