miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients

Abstract

Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the miR-7 methylation status with the cisplatin treatment response. Our results analyzed in 81 samples show that miR-7 methylation is a common event in tumor tissue and it is more frequent as the stage of the disease advances, remaining in 75% of metastatic patients. Tumor miR-7 unmethylation trend to a better PFS in early stages, and when our data was validated in an extended “ in silico” cohort of 969 patients we obtained a significant increment in PFS and OS in those patients harboring miR-7 unmethylated (p = 0.010 and p = 0.007 respectively). When we select those early-stages patients harbouring miR-7 methylation, we observed that adenocarcinoma patients present a dramatic decrease in PFS compared with squamous cell carcinoma patients (median 18.9 versus 59.7 months, p = 0.002). In conclusion, our results show that presence of miR-7 methylation in early-stage NSCLC is suggestive of aggressive behavior, especially for adenocarcinoma patients. One major challenge in early diagnosis in NSCLC is identify the subgroup of patients that could benefit for adjuvant therapy, our data establish the basis for epigenetic classification on early-stage NSCLC that could influence treatment decisions in the future. Electronic supplementary material The online version of this article (10.1186/s13578-019-0326-7) contains supplementary material, which is available to authorized users.

The role of miR-6884-5p in epithelial-mesenchymal transition in non-small cell lung cancer

“…There are some candidate miRNAs in NSCLC that can be used as oncogenic or tumor suppressor factors, and abnormal miRNA levels may serve as useful biomarkers for NSCLC diagnosis [ 19 , 20 ]. For example, miR-7 regulates apoptosis and malignant behavior of HeLa and C33A cells by targeting XIAP in lung cancer [ 35 , 36 ]. Moreover, upregulating miR-145 is associated with the aggressive progression and poor prognosis of NSCLC patients [ 37 ].…”

When Oxidative Stress Meets Epigenetics: Implications in Cancer Development

“…These cisplatin-resistant cell lines share a common downregulation of miR-7 expression, compared to the parental sensitive cells, due to the hypermethylation of a CpG island located on its promoter [ 150 ]. Most importantly, lung adenocarcinoma patients harbor a hypermethylated miR-7 promoter when compared to healthy controls [ 193 ]. In addition, these patients show lower overall and progression-free survival rates, suggesting that the hypermethylation of miR-7 could be involved in the early establishment of the disease [ 193 ].…”

“…Most importantly, lung adenocarcinoma patients harbor a hypermethylated miR-7 promoter when compared to healthy controls [ 193 ]. In addition, these patients show lower overall and progression-free survival rates, suggesting that the hypermethylation of miR-7 could be involved in the early establishment of the disease [ 193 ]. In fact, miR-7 hypermethylation constitutes a molecular event that accounts mainly at the expense of the emphysema patients, as analyzed from a huge COPD cohort.…”

Overview of host miRNA properties and their association with epigenetics, long non-coding RNAs, and Xeno-infectious factors

“…Another miRNA involved in gastric cancer invasion is miR-7-5p that its silencing by methylation of its promoter leads to an increase in its target genes, namely Smo and Hes1 [ 135 ]. Furthermore, the promoter methylation of miR-7 is a significant and early-stage biomarker in cisplatin-resistance and clinical management of ovarian and lung cancer cells [ 136 ] (Table 2 ).…”