Wang Ouxi, Shi Di, Li Yaqi, Zhou Xiaoyan, Yan Haidan, Yao Qianlan
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China.
Front Oncol. 2022 Aug 17;12:912882. doi: 10.3389/fonc.2022.912882. eCollection 2022.
Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer.
Based on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR).
A biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes.
We identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer.
结直肠癌的早期诊断可显著改善预后并降低死亡率。然而，活检样本的病理诊断中常常会遇到诊断不明确的情况。长链非编码RNA（lncRNA）的异常表达与结直肠癌的发生和发展相关。探索lncRNAs作为结直肠癌的候选诊断生物标志物具有重要价值和临床意义。
基于lncRNA对的样本内相对表达水平，我们鉴定出一组结直肠癌的候选诊断生物标志物。此外，我们在不同实验室和不同平台产生的独立数据集中对其进行了验证。我们还使用定量实时聚合酶链反应（RT-qPCR）在结直肠癌组织样本中对其进行了检测。
鉴定出一种由六个lncRNA对（包括九个lncRNAs）组成的生物标志物用于结直肠癌的诊断。对于总共950个癌症样本和247个非癌症样本，敏感性和特异性均可达到约90%。对于腺瘤样本，准确率可达到73%。对于炎症性肠病患者的正常组织，93%（14/15）被正确分类为非癌症。此外，lncRNA对生物标志物在所有临床阶段均表现出优异的性能；即使在早期阶段，I期和II期的准确率也可分别达到87%和82%。同时，该生物标志物对微卫星不稳定性状态也具有较强的稳健性。更重要的是，我们使用定量实时聚合酶链反应（RT-qPCR）在35个结直肠癌组织样本和30个癌旁组织样本中检测了该生物标志物。准确率可达到93.3%（70/75）。特别地，即使在早期肿瘤（I期和II期）中，准确率也可达到90.9%（30/33）。富集分析表明，这些lncRNAs参与了高度相关的癌症通路和免疫相关通路。免疫分析表明，这些标记lncRNAs与多种免疫细胞相关，这意味着它们可能参与了结直肠癌中免疫细胞功能的调节。大多数生物标志物lncRNAs在结直肠癌驱动基因的突变组和野生型组之间也存在差异表达。
我们鉴定并验证了由九个lncRNAs组成的六个lncRNA对作为辅助诊断结直肠癌的生物标志物。
