Medical School of Nantong University, Nantong University, Nantong, China.
Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, China.
Mol Med. 2022 Jun 11;28(1):63. doi: 10.1186/s10020-022-00491-8.
Gastric cancer (GC) is one of the diseases that endanger human health with high morbidity and mortality. The positive rates of traditional biomarkers in the diagnosis of GC are low, so it is necessary to find biomarkers with high sensitivity to increase the detection rate. tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs with specific biological functions and aberrant expression in cancer. In this study, we focused on the potential of tRNA-derived small RNAs as GC biomarkers.
The differentially expressed tsRNAs in three pairs of GC tissues were screened with high-throughput sequencing and verified using the TCGA database and Quantitative real-time PCR. The methodological evaluation of tRF-23-Q99P9P9NDD was verified by agarose gel electrophoresis, RIN evaluation, and Sanger sequencing. The Chi-square test was used to evaluate the relationship between the tRF-23-Q99P9P9NDD expression and clinicopathological parameters. Kaplan-Meier survival analysis was used to evaluate the effect of the tRF-23-Q99P9P9NDD expression on survival. Additionally, the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of tRF-23-Q99P9P9NDD in GC.
Differential expression of serum tRF-23-Q99P9P9NDD could distinguish GC patients from gastritis patients and healthy donors. Chi-square test showed that high expression of tRF-23-Q99P9P9NDD was significantly associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion. Kaplan-Meier curve showed that patients with high expression of tRF-23-Q99P9P9NDD had a lower survival rate than patients with low expression of this biomarker. ROC analysis showed that, compared with conventional biomarkers, the efficacy of tRF-23-Q99P9P9NDD was higher, which was improved by the combination of biomarkers, and even in the early stages. Finally, we preliminarily predicted the downstream of tRF-23-Q99P9P9NDD in GC cells.
The expression of tRF-23-Q99P9P9NDD in GC serum can identify GC patients, and it has higher efficacy than conventional biomarkers even in the early stages. Furthermore, tRF-23-Q99P9P9NDD can monitor the postoperative conditions of GC patients.
胃癌（GC）是一种发病率和死亡率都很高的危害人类健康的疾病。传统生物标志物在 GC 诊断中的阳性率较低，因此有必要寻找具有高灵敏度的生物标志物来提高检出率。tRNA 衍生的小 RNA（tsRNAs）是一类具有特定生物学功能的新型小非编码 RNA，在癌症中表达异常。在本研究中，我们专注于 tsRNAs 作为 GC 生物标志物的潜力。
通过高通量测序筛选 3 对 GC 组织中的差异表达 tsRNAs，并通过 TCGA 数据库和定量实时 PCR 进行验证。通过琼脂糖凝胶电泳、RIN 评估和 Sanger 测序验证 tRF-23-Q99P9P9NDD 的方法学评估。采用卡方检验评估 tRF-23-Q99P9P9NDD 表达与临床病理参数的关系。采用 Kaplan-Meier 生存分析评估 tRF-23-Q99P9P9NDD 表达对生存的影响。此外，采用受试者工作特征曲线（ROC）评估 tRF-23-Q99P9P9NDD 在 GC 中的诊断效能。
血清 tRF-23-Q99P9P9NDD 的差异表达可区分 GC 患者与胃炎患者和健康供者。卡方检验显示，tRF-23-Q99P9P9NDD 高表达与 T 分期、淋巴结转移、TNM 分期和神经/血管侵犯显著相关。Kaplan-Meier 曲线显示，tRF-23-Q99P9P9NDD 高表达患者的生存率低于低表达患者。ROC 分析显示，与传统生物标志物相比，tRF-23-Q99P9P9NDD 的效能更高，通过联合标志物甚至在早期阶段可提高其效能。最后，我们初步预测了 GC 细胞中 tRF-23-Q99P9P9NDD 的下游靶标。
GC 血清中 tRF-23-Q99P9P9NDD 的表达可识别 GC 患者，其效能高于传统生物标志物，甚至在早期阶段。此外，tRF-23-Q99P9P9NDD 可监测 GC 患者的术后情况。
