The online version of this article (doi:10.1186/1477-7819-10-225) contains supplementary material, which is available to authorized users.
The authors had no conflicts of interest to declare in relation to this article.
KL and TQ carried out the molecular genetic studies, participated in the sequence alignment, and drafted the manuscript. JW and JR carried out the immunoassays. HHY participated in the sequence alignment. LMT participated in the design of the study and performed the statistical analysis. KL and LMT conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
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.
Authors’ original file for figure 112957_2012_1110_MOESM1_ESM.tiff
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- Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer
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