ABSTRACT
Objective:To assess the association between preoperative neutrophil–lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell distribution width (RDW) and the tumor pathological features in gastric cancer (GC) patients. Methods: We re-viewed the records of 434 patients from 2012 to 2014 in Fujian Cancer Hospital. All patients were admitted to the hospital for the first time, and no patients received any cancer-specific pretreatment. For comparison, 309 age-and gender-matched healthy individuals who underwent annual physical examination at the hospital and 342 patients with chronic atrophic gastritis were enrolled. Results:GC patients had higher NLR, PLR, and RDW than the controls (P<0.000 1). Elevated NLR, PLR, and RDW were associated with the develop-ment of tumor stages as indicated by the Kruskal-Wallis analysis. However, no similar association was observed between the tumor dif-ferentiation grade and location and those three markers. Multivariate regression analysis further revealed that both NLR and PLR were independent predicting factors for either the tumor TNM or T stage (P<0.000 1). ROC curve analysis showed that NLR and PLR had a certain diagnostic effect on the preoperative T staging of GC. Conclusion:The preoperative NLR and PLR levels are closely correlated with the tumor TNM stages in GC patients. Both these parameters have potential values as markers to assist either in early diagnosis or preoperative tumor stage evaluation in GC.
ABSTRACT
Objective: To investigate the role of microRNA-375 (miR-375) in the occurrence of trastuzumab-resistance in human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells through regulating epithelial-mesenchymal transition (EMT). Methods: The sensitivities of HER2-positive breast cancer cell lines SK-BR-3 (a parental sensitive cell line) and SK-BR-3R (a trastuzumab-resistant cell line) to trastuzumab were detected by MTT assay. The expression levels of miR-375 and EMT-associated proteins E-cadherin and vimentin in the two cell lines were detected by real-time fluorescent quantitative PCR and Western blotting, respectively. After miR-375 mimic was transfected into SK-BR-3R cells, the changes of miR-375, E-cadherin and vimentin expression levels were detected by real-time fluorescent quantitative PCR and Western blotting, and the change of trastuzumab sensitivity of SK-BR-3R cells was detected by MTT method. The potential target genes of miR-375 were predicted by bioinformatics software, and metadherin (MTDH) was selected as one of target genes. Luciferase reporter assay was conducted to verify the role of miR-375 in regulation of MTDH gene transcription. In addition, the changes of E-cadherin and vimentin expression levels in SK-BR-3R cells after transfection with MTDH siRNA were detected by Western blotting. Results: Compared to the sensitive SK-BR-3 cells, the sensitivity of SK-BR-3R cells to trastuzumab decreased significantly (P < 0.001), and the expression levels of miR-375 (P < 0.001) and vimentin (P < 0.05) were significantly down-regulated, but the level of EMT marker E-cadherin was significantly up-regulated (P < 0.05). After transfection with miR-375 mimic, the expression levels of miR-375 (P < 0.001) and vimentin (P < 0.01) were up-regulated, while the level of E-cadherin was down-regulated (P < 0.001); the trastuzumab sensitivity of SK-BR-3R cells was increased (P < 0.001). A negative regulatory effect of miR-375 on the transcription of MTDH gene was observed (P < 0.001). After MTDH-siRNA transfection, the expressions of MTDH and vimentin were down-regulated (both P < 0.001), while the expression of E-cadherin was up-regulated (P < 0.001). Conclusion: miR-375 plays a role in drug-resistance of HER2-positive breast cancer cells to trastuzumab through regulating EMT, which is related to the target regulation of MTDH gene expression.