Figure 1: miR-128-3p overexpression in NSCLC specimens correlates with poor patient survival, disease progression and chemotherapy failure.

(a) Schematic representation for the establishment of a chemoresistant subcutaneous tumour model. Mice bearing A549-luc xenografts were intraperitoneally injected with the first round of CDDP treatment (CDDP-1st) or control treatment (Ctrl-1st), and cells were isolated from the resultantly remaining tumours, cultured and re-transplanted, followed by a second round of CDDP treatment (CDDP-2nd) or control treatment (Ctrl-2nd) and so ons. (b) Tumour volume of subcutaneous tumours at the indicated rounds of CDDP or Ctrl treatment. (c) Lung tissues obtained from mice bearing NSCLC xenografts at the fourth round of Ctrl and CDDP treatment were histologically examined. Scale bar, 100 μm. (d) Tumour-derived cultured cells from Ctrl-4th and CDDP-4th treatment were subjected to miRNA array analysis, revealing the top 10 upregulated miRNAs in chemoresistant, metastatic A549-luc-CDDP-4th cells. Intensity values representing miRNA expression levels were log10 transformed. (e) Expression of miR-128-3p in human lung cancer clinical specimens using the TCGA microRNA Hiseq expression array data. (f) Absolute real-time PCR using a standard curve of miR-128-3p expression in adjacent normal lung tissues and the indicated NSCLC specimens. Error bars represent mean±s.d. derived from three independent experiments. A two-tailed Student’s t-test was used for statistical analysis (*P<0.05). (g) Kaplan–Meier analysis of OS of a cohort of 153 NSCLC patients at all stages and late stages III–IV. Each subgroup was divided into the low- (below or equal to the median value) and high-miR-128-3p expression groups (above the median value). (h) Kaplan–Meier analysis of OS and PFS of a cohort of 234 NSCLC patients (stage I, n=27; stage II, n=65; stage III, n=52; stage IV, n=90) receiving CDDP-based first-line treatment who were divided into high (>median, n=117) and low (<median, n=117) miR-128-3p expression groups. (i) Expression levels of miR-128-3p in NSCLC patients subgrouped by curative responsiveness to chemotherapy, including PR, SD and PD, according to the RECIST. Ordinate utilizes the logarithmic scale (log10). *P<0.05, **P<0.01. (j) Correlation of miR-128-3p expression level with curative responsiveness of NSCLC patients to chemotherapy. RECIST, Response Evaluation Criteria in Solid Tumours.