Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer
1 Department of General Surgery, Changzhou No. 2 Hospital, Nanjing Medical University, Nanjing, China
2 Department of General Surgery, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China
World Journal of Surgical Oncology 2012, 10:225 doi:10.1186/1477-7819-10-225Published: 29 October 2012
MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC), and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction.
Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs), using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS) was also investigated.
Let-7i was significantly down-regulated in most tumor tissues (78/86: 91%) compared with paired NATs (P < 0.001), and low levels of let-7i were significantly correlated with local invasion, lymphatic metastasis, and poor pathologic tumor response. Multivariate Cox regression analysis revealed that low let-7i expression was an unfavorable prognostic factor of OS (hazard ratio (HR) = 2.316, P =0.024) independently of other clinicopathological factors, including tumor node metastasis (TNM) stage (HR = 3.226, P = 0.013), depth of infiltration (HR = 4.167, P < 0.001), and lymph node status (HR = 2.245, P = 0.037).
These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.