Association of Mps one binder kinase activator 1 (MOB1) expression with poor disease-free survival in individuals with non-small cell lung cancer

Abstract

Background: Mps one binder kinase activator 1 (MOB1) is a core component of the Hippo signaling pathway and has been implicated as a tumor suppressor. Here, we evaluated the possible relationship of MOB1 expression in non-small cell lung cancer (NSCLC) to prognosis.

Methods: We retrospectively analyzed 205 lung adenocarcinoma patients treated at Kyushu University Hospital between November 2007 and October 2012. MOB1 expression in tumor cells of surgical specimens was evaluated by immunohistochemistry. Invasive activity of NSCLC cell lines in vitro was measured with a transwell assay.

Results: Expression of MOB1 was classified as high in 105 of the 205 (51.2%) tumor specimens, and such high expression was significantly associated with poor disease-free survival (P = 0.0161). Among the various clinicopathologic parameters examined, high MOB1 expression was significantly associated only with intratumoral vascular invasion (P = 0.0005). Multivariate analysis also identified high MOB1 expression as a significant independent risk factor for disease-free survival (P = 0.0319). The invasiveness of H1299 cells in vitro was increased or attenuated by overexpression or knockdown of MOB1, respectively.

Conclusions: Our results suggest that MOB1 might promote early recurrence of NSCLC by increasing vascular invasion by tumor cells.

Key points: SIGNIFICANT FINDINGS OF THE STUDY: We found that high MOB1 expression in surgical specimens of lung adenocarcinoma was associated with poor disease-free survival and with intratumoral vascular invasion. MOB1 expression also promoted the invasiveness of NSCLC cells in vitro.

What this study adds: Our results thus suggest that high MOB1 expression is a risk factor for early postoperative recurrence in lung adenocarcinoma.

Keywords: Hippo pathway; MOB1; immunohistochemistry; lung adenocarcinoma; vascular invasion.

Figure 1

Representative immunohistochemical staining of MOB1 in lung adenocarcinoma specimens. Specimens negative (score = 0) (a and b) or positive (score = 4) (c and d) for MOB1 staining are shown at low (a and c) and high (b and d) magnification. Scale bars: 100 μm (a and c) or 50 μm (b and d).

Figure 2

Kaplan‐Meier analysis of (a) disease‐free survival; and (b) overall survival for lung adenocarcinoma patients (n = 205) according to expression of MOB1 in tumor tissue (low or high) ( ) MOB1 low expression, ( ) MOB1 high expression. The P‐values were determined by the log‐rank test.

Figure 3

Effects of MOB1 expression level on tumor cell invasiveness in vitro. (a–d) Immunoblot analysis of MOB1 and β‐actin (loading control) in H1299 cells (a and b) or PC9 cells (c and d) that had been transfected either with an expression vector for MOB1A or the corresponding empty vector (control) (a and c) or with MOB1A/B or control siRNAs (b and d). (e–h) Cells as in (a) to (d), respectively, were assayed for invasion activity in vitro. Representative staining of invading cells on the lower side of the membrane is shown. Scale bars, 100 μm. (i–l) Percent invasion determined for cells as in (e) to (h), respectively. Data are means ± SD from three independent experiments. The P‐values were determined by Student's t‐test. **P < 0.01.