Clinicopathological significance of NMIIA overexpression in human gastric cancer

Abstract

Altered expressions of nonmuscle myosin IIA (NMIIA) have been observed in certain types of cancers, but the impact of the alterations in gastric cancer (GC) remains unclear. The purpose of this study was to evaluate the expression of NMIIA at the mRNA and protein level in patients with GC and to assess its clinical significance. We investigated the expression of NMIIA in fresh, paired GC tissues by reverse transcriptase polymerase chain reaction (RT-PCR; n = 14) and Western blot analysis (n = 36). Simultaneously, we performed immunohistochemistry (IHC) on paraffin embedded specimens, including 96 GC specimens, 30 matched normal specimens and 30 paired metastatic lymph node samples. NMIIA is overexpressed in GC compared with the adjacent normal gastric epithelium (p < 0.001) and high-level NMIIA expression is significantly correlated with the depth of wall invasion, lymph node metastasis, distant metastasis and Tumor Node Metastasis (TNM) stage. Furthermore, elevated NMIIA expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.021). These findings indicate that overexpression of NMIIA may contribute to the progression and poor prognosis of GC.

Figure 1

Overexpression of NMIIA in GC as detected by semiquantitative RT-PCR. Data presented here is a representative of all the samples. GAPDH was used as internal control. N indicates normal tissue; C, patient-matched tumor tissue.

Figure 2

Overexpression of NMIIA in GC as detected by Western blot analysis. Data presented here is a representative of all the samples. β-actin was used as a loading control. N indicates normal tissue; C, patient-matched tumor tissue.

Figure 3

Immunohistochemical analysis of NMIIA expression in gastric carcinoma and adjacent normal gastric epithelium (200×). (A) Intestinal type gastric carcinoma; (B) Diffuse type gastric carcinoma. (a) Weak staining detected in tumor cells; (b) Moderate staining observed in tumor cells; (c) Strong staining detected in tumor cells.

Figure 4

A gastric carcinoma sample shows weak NMIIA expression (a); but its metastatic lymph node has strong NMIIA expression (b) (200×). (A) Intestinal type gastric carcinoma; (B) Diffuse type gastric carcinoma.

Figure 5

(A) The mean overall survival time for the high NMIIA expression group was 48.5 months, and for the low NMIIA expression group was 67.6 months (p < 0.001); (B) In R0 (radical operation) gastric cancer, the mean overall survival time for the high NMIIA expression group was 51.7 months and for the low NMIIA expression group was 69.8 months (p = 0.005); Statistical significance of the difference between curves of NMIIA high-expressing and low-expressing patients was compared within subgroups of TNM stage I + II (p = 0.012; C) and III + IV (p = 0.027; (D). No statistical significance of the difference between curves of NMIIA high-expressing and low-expressing patients was compared within subgroups of intestinal type gastric carcinoma (p = 0.071; E) and diffuse type gastric carcinoma (p = 0.112; F).

Figure 5

(A) The mean overall survival time for the high NMIIA expression group was 48.5 months, and for the low NMIIA expression group was 67.6 months (p < 0.001); (B) In R0 (radical operation) gastric cancer, the mean overall survival time for the high NMIIA expression group was 51.7 months and for the low NMIIA expression group was 69.8 months (p = 0.005); Statistical significance of the difference between curves of NMIIA high-expressing and low-expressing patients was compared within subgroups of TNM stage I + II (p = 0.012; C) and III + IV (p = 0.027; (D). No statistical significance of the difference between curves of NMIIA high-expressing and low-expressing patients was compared within subgroups of intestinal type gastric carcinoma (p = 0.071; E) and diffuse type gastric carcinoma (p = 0.112; F).