Zhu Jinfeng, Huang Qian, Peng Xingyu, Luo Chen, Liu Sicheng, Liu Zitao, Wu Xun, Luo Hongliang
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
Front Oncol. 2022 Mar 29;12:799475. doi: 10.3389/fonc.2022.799475. eCollection 2022.
Genomic instability (GI) is a critical feature of cancer which plays a key role in the occurrence and development of pancreatic adenocarcinoma (PAAD). Long non-coding RNA (LncRNA) is an emerging prognostic biomarker because it is involved in regulating GI. Recently, researchers used such GI-related LncRNAs (GILncRNAs) to establish a prognostic signature for patients with cancer and helped in predicting the overall prognosis of the patients. However, it is evident that patients with PAAD still lack such prognostic signature constructed with GILncRNA.
The present study screened GILncRNAs from 83 patients with PAAD. Prognosis-related GILncRNAs were identified by univariate Cox regression analysis. The correlation coefficients of these GILncRNAs were obtained by multivariate Cox regression analysis and used to construct a signature. The signature in the present study was then assessed through survival analysis, mutation correlation analysis, independent prognostic analysis, and clinical stratification analysis in the training set and validated in the testing as well as all TCGA set. The current study performed external clinical relevance validation of the signature and validated the effect of AC108134.2 in GILncSig on PAAD using experiments. Finally, the function of GILncRNA signature (GILncSig) dependent on Gene Ontology enrichment analysis was explored and chemotherapeutic drug sensitivity analysis was also performed.
Results of the present study found that a total of 409 GILncRNAs were identified, 5 of which constituted the prognostic risk signature in this study, namely, AC095057.3, AC108134.2, AC124798.1, AL606834.1, and AC104695.4. It was found that the signature of the present study was better than others in predicting the overall survival and applied to patients with PAAD of all ages, genders, and tumor grades. Further, it was noted that the signature of the current study in the GSE102238, was correlated with tumor length, and tumor stage of patients with PAAD. , functional experiments were used in the present study to validate that AC108134.2 is associated with PAAD genomic instability and progression. Notably, results of the pRRophetic analysis in the current study showed that the high-risk group possessed reverse characteristics and was sensitive to chemotherapy.
In conclusion, it was evident that the GILncSig used in the present study has good prognostic performance. Therefore, the signature may become a potential sensitive biological indicator of PAAD chemotherapy, which may help in clinical decision-making and management of patients with cancer.
基因组不稳定（GI）是癌症的一个关键特征，在胰腺腺癌（PAAD）的发生和发展中起关键作用。长链非编码RNA（LncRNA）是一种新兴的预后生物标志物，因为它参与调节基因组不稳定。最近，研究人员使用这些与基因组不稳定相关的LncRNA（GILncRNA）为癌症患者建立了一个预后特征，并有助于预测患者的总体预后。然而，显然PAAD患者仍然缺乏用GILncRNA构建的这种预后特征。
本研究从83例PAAD患者中筛选GILncRNA。通过单因素Cox回归分析确定与预后相关的GILncRNA。通过多因素Cox回归分析获得这些GILncRNA的相关系数，并用于构建一个特征。然后在训练集中通过生存分析、突变相关性分析、独立预后分析和临床分层分析对本研究中的特征进行评估，并在测试集以及所有TCGA数据集中进行验证。本研究对该特征进行了外部临床相关性验证，并通过实验验证了AC108134.2在GILncSig中对PAAD的作用。最后，通过基因本体富集分析探索了GILncRNA特征（GILncSig）的功能，并进行了化疗药物敏感性分析。
本研究结果发现，共鉴定出409个GILncRNA，其中5个构成了本研究中的预后风险特征，即AC095057.3、AC108134.2、AC124798.1、AL606834.1和AC104695.4。发现本研究的特征在预测总体生存方面优于其他特征，适用于所有年龄、性别和肿瘤分级的PAAD患者。此外，注意到本研究在GSE102238中的特征与PAAD患者的肿瘤长度和肿瘤分期相关。本研究使用功能实验验证AC108134.2与PAAD基因组不稳定和进展相关。值得注意的是，本研究的pRRophetic分析结果表明，高危组具有相反的特征，对化疗敏感。
总之，显然本研究中使用的GILncSig具有良好的预后性能。因此，该特征可能成为PAAD化疗的一个潜在敏感生物指标，这可能有助于癌症患者的临床决策和管理。
