Negative correlation of cytoplasm TIMP3 with miR-222 indicates a good prognosis for NSCLC

Abstract

Background: The aim of this study was to observe the expression of microRNA-222 (miR-222) and matrix metalloproteinase inhibitor 3 (TIMP3) in non-small cell lung cancer (NSCLC) and discuss their significance. Methods: A total of 230 patients with NSCLC were enrolled in the observation group during the operation. Ninety-eight normal adjacent tissues were used as the control group. Two groups of miR-222 and TIMP3 were detected by in situ hybridization and immunohistochemistry. The distribution of miR-222 and TIMP3 in A549/H358/PC9 cells was observed by immunofluo-rescence. Chi-squared and Spearman correlation tests were used to analyze the relationship among miR-222, TIMP3 expression, and clinicopathological parameters of NSCLC. Kaplan– Meier and Cox proportional hazards regression were used to analyze the prognostic impact of miR-222 and TIMP3. Results: Immunohistochemistry showed that the expression of miR-222 in lung cancer tissue was significantly higher, but TIMP3 was lower than that in normal lung tissue (P = 0.0001 for the former and P = 0.0002 for the latter). Meanwhile, miR-222 and TIMP3 were mainly distributed in the cytoplasm. Among them, cTIMP3 accounted for 70.29% (72/101), cmiR-222 for 59.35% (92/155), 14.85% for nTIMP3 (15/101), and 18.06% for nmiR-222 (28/155). There was a significant difference in distribution (both P < 0.0001). The expression of miR-222 and TIMP3 were negatively correlated in lung cancer tissues (r =-0.43, P = 0.0219). With the progression of clinical stage, the positive intensity of cTIMP3 showed a decreasing trend, while the cmiR-222 showed a reverse trend (the former P = 0.0024 and the latter P < 0.0001). In the Kaplan–Meier prognostic analysis, we found that the high expression of cTIMP3 could predict a better prognosis (P = 0.0040), whereas cmiR-222 was the opposite (P = 0.0016). Multivariate analysis shows that both can be used as independent factors. Conclusion: TIMP3 expression in lung cancer is relatively low and has a negative correlation with lung cancer staging and prognosis, suggesting that it may play a defensive function in the development of lung cancer, while miR-222 has the opposite effect, and the expression of both proteins is negatively correlated, suggesting that in lung cancer progresses, both proteins may play some role together.