Department of Pulmonology, ''Dharmais'' Hospital National Cancer Center, Jakarta 11420, Indonesia.
Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
Zhongguo Fei Ai Za Zhi. 2020 May 20;23(5):321-332. doi: 10.3779/j.issn.1009-3419.2020.104.02. Epub 2020 Apr 14.
Lung cancer is the most common cause of death in men in the world and in Indonesia where non-small cell carcinoma lung cancer (NSCLC) constitutes 85% of all lung cancer cases. The high mortality rate is due to a poor prognosis and is often diagnosed as having advanced stages. If it is known at the initial stage, the prognosis of lung cancer will be better. Prognosis can be predicted with a marker of prognostic biology, one of which is micro RNA (miRNA). This study aims to prove that serum miRNA can be predictive biological marker and prognosis in NSCLC patients in Indonesia.
This study was cohort retrospective among 52 subjects in "Dharmais" Hospital National Cancer Center. Sample was obtained from patients' serum. MiR-34, miR-148, miR-155 and miR-222 serum are measured through Real-Time PCR (qPCR). Data were analyzed and interpreted with descriptive analysis, bivariate analysis (Mann Whitney-U for two type of variables or Kruskal-Wallis for more than two type of variables. Kaplan-Meier analysis was used to know association between characteristic which are sociodemographic, performance status, clinico-pathology, and survival rate in miRNA expression.
From this study, miRNA expression: miR-34 (46.15%), miR-148 (23.08%), miR-155 (40.38%) and miR-222 (32.69%). Performance status score was statistically significant correlation with miR-148 (P=0.049) and miR-222 (P=0.018). High miR-34 is associated with multiple M1b metastatic type (P=0.020), cancer cell type (adenocarcinoma, P=0.009) and adenocarcinoma epidermal growth factor receptor (EGFR) mutation (negative, P=0.031). There was a significant correlation between the high miR-222 as a poor prognosis in advanced stage NSCLC with M1b metastasis (Median Survival/MS: 27 d, P=0.049) and positive EGFR mutations (MS: 74 d, P=0.049) and correlation of miR-155 with adenocarcinoma (MS: 69 d, P=0.034) and positive EGFR gene mutations (MS: 58 d, P=0.023).
High miR-34 expression in advanced stage NSCLC is the predictive factor for multiple metastatic, adenocarcinoma cell type and adenocarcinoma negative EGFR mutation. High expression of miR-155 and miR-222 are poor prognoses, especially high miR-222 found in metastasis M1b and positive EGFR mutation and miR-155 found in adenocarcinoma and positive EGFR gene mutations. Further studies regarding correlation between miRNA and survival rate are needed.
肺癌是全球男性和印度尼西亚人群中最常见的死亡原因，非小细胞肺癌（NSCLC）占所有肺癌病例的 85%。高死亡率归因于预后不良，且通常被诊断为晚期。如果在早期阶段发现，肺癌的预后将更好。预后可以通过预后生物学标志物来预测，其中之一是 microRNA（miRNA）。本研究旨在证明血清 miRNA 可作为 NSCLC 患者的预测性生物标志物和预后指标。
这是一项在“Dharmais”国家癌症中心进行的队列回顾性研究，共纳入 52 名受试者。样本取自患者的血清。通过实时 PCR（qPCR）测量 miR-34、miR-148、miR-155 和 miR-222 血清水平。通过描述性分析、双变量分析（Mann Whitney-U 用于两种类型的变量或 Kruskal-Wallis 用于三种或三种以上类型的变量）和 Kaplan-Meier 分析来分析和解释数据。Kaplan-Meier 分析用于了解 miRNA 表达与特征（包括社会人口统计学、表现状态、临床病理学和生存率）之间的关联。
本研究中，miRNA 表达情况为：miR-34（46.15%）、miR-148（23.08%）、miR-155（40.38%）和 miR-222（32.69%）。表现状态评分与 miR-148（P=0.049）和 miR-222（P=0.018）呈显著相关。高 miR-34 与多种 M1b 转移性类型（P=0.020）、癌细胞类型（腺癌，P=0.009）和腺癌表皮生长因子受体（EGFR）突变（阴性，P=0.031）相关。高 miR-222 与晚期 NSCLC 的 M1b 转移（中位生存时间[MS]：27d，P=0.049）和阳性 EGFR 突变（MS：74d，P=0.049）呈显著负相关，与 miR-155 与腺癌（MS：69d，P=0.034）和阳性 EGFR 基因突变（MS：58d，P=0.023）呈显著相关。
晚期 NSCLC 中高表达 miR-34 是多个转移、腺癌细胞类型和腺癌阴性 EGFR 突变的预测因素。高表达 miR-155 和 miR-222 提示预后不良，尤其是在 M1b 转移和阳性 EGFR 突变中发现高 miR-222，在腺癌和阳性 EGFR 基因突变中发现 miR-155。需要进一步研究 miRNA 与生存率之间的关系。
