miR-99a-5p as Possible Diagnostic and Prognostic Marker in Patients With Gastric Cancer
miR-99a-5p as Possible Diagnostic and Prognostic Marker in Patients With Gastric Cancer
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DOI：
10.1016/j.jss.2020.01.004
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发表时间：
2020-06-01
影响因子：
2.2
通讯作者：
Ichikawa，Daisuke
中科院分区：
文献类型：
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作者：
Saito，Ryo;Maruyama，Suguru;Ichikawa，Daisuke
背景：印戒细胞癌（SRC）是胃癌的组织学亚型之一，在临床实践中经常表现出侵袭性行为，因此是晚期胃癌中常见的亚型。然而，SRC，特别是在早期阶段，最近有报道显示其恶性肿瘤的可能性低于其他病理亚型。由于SRC病理的详细分子机制尚不清楚，我们将重点放在了microRNAs （miRs）上，旨在阐明赋予早期SRC特征的分子机制。材料与方法采用福尔马林固定石蜡包埋的方法，对包括SRC在内的各种病理亚型胃癌患者进行纯化并评价mir。结果正如预期的那样，SRC患者的miR-99a-5p表达显著升高。此外，研究发现miR-99a-5p的高表达与侵袭性较低的临床病理特征密切相关，并且通过miR-99a-5p的过表达对两种SRC细胞系的增殖抑制进行了功能研究。本研究报道，在SRC患者中观察到高水平的miR-99a-5p，特别是早期SRC患者。此外，我们发现miR-99a-5p的表达与细胞增殖有关。因此，miR-99a-5p可能成为早期SRC和患者淋巴结转移或相关不良预后的诊断性生物标志物。
BackgroundThe signet-ring cell carcinoma (SRC), one of the histological subtypes of gastric cancer, often exhibits aggressive behavior in clinical practice and is therefore a commonly found subtype in advanced gastric cancer. However, SRC, especially at the early stages, has recently been reported to show a lower potential for malignancy than other pathological subtypes. Because the detailed molecular mechanisms underlying SRC pathology remain unclear, we focused on microRNAs (miRs) and aimed to elucidate the molecular mechanisms involved in endowing early SRC with its characteristic properties.Materials and methodsFormalin-fixed paraffin-embedded samples of patients diagnosed with various pathological subtypes of gastric cancer including SRC were used to purify and subsequently evaluate miRs.ResultsAs expected, patients with SRC were observed to have significantly high miR-99a-5p expression. Further, high miR-99a-5p expression was found to closely correlate with less aggressive clinicopathological features, and functional studies probed by overexpression of miR-99a-5p resulted in inhibition of proliferation in two SRC cell lines.ConclusionsThe present study reports that high levels of miR-99a-5p were observed in patients with SRC, particularly those with early stage SRC. In addition, miR-99a-5p expression was found to be related to cell proliferation. Therefore, miR-99a-5p could emerge as a diagnostic biomarker for early SRC and lymph node metastases or related adverse prognosis in patients.