Aim: Cancer-associated fibroblasts (CAFs) are closely related to epithelial-mesenchymal transition (EMT) and chemoresistance in various cancers. Patients & methods: Experiments in vivo and retrospe...

Carcinoma‑associated fibroblasts (CAFs) are the major components of mesenchymal cells in the inflammatory tumor microenvironment. They are involved in epithelial‑mesenchymal transition (EMT) and chemotherapy resistance by directly contacting with cancer cells or secretory cytokines. In the present study, we examined the role of CAFs in the induction of EMT in ovarian cancer. Primary ovarian cancer cells, CAFs and normal fibroblasts (NFs) were isolated from fresh cancer tissue and cultured for immunohistochemistry studies. Enzyme‑linked immunosorbent assay (ELISA) was used to detect the expression of IL‑6 in the culture supernatants of these cells. The expression of IL‑6 at the mRNA level was examined by RT‑PCR. The expression of IL‑6 at the protein level in ovarian cancer tissues was determined using an immunofluorescence assay in both tissue sections and cell lobes. OVCAR3 cells were treated with the culture supernatants collected from CAFs and NFs. IL‑6 monoclonal antibody (mAb) was employed to neutralize IL‑6. The expression of phosphorylated STAT3 was assessed. Changes in EMT, proliferation, invasion and proapoptotic protein expression were also examined. Flow cytometry was performed to detect the changes in apoptosis resistance of OVCAR3 cells. The JAK2/STAT3 pathway‑specific inhibitor AG490 was used to block this pathway and the β‑TGF inhibitor was used to inhibit EMT. The clinical data of patients treated in our hospital were collected between January 1st, 2009 and June 30th, 2013. The expression of interstitial IL‑6 in paraffin‑embedded tissues was detected by immunohistochemistry. The relationship between the expression of interstitial IL‑6 and the treatment response was examined by linear regression and multiple linear regression analyses. We found that CAFs were the main source of IL‑6 in ovarian cancer tissue. CAFs promoted the phosphorylation of STAT3 in ovarian cancer and enhanced the proliferation, invasion and EMT. Enhanced EMT may lead to apoptosis resistance, inhibitory expression of pro‑apoptotic proteins and paclitaxel resistance. A total of 255 patients were enrolled in this retrospective study. Univariate and multivariate analyses revealed that age, CA125, interstitial IL‑6 expression and cytoreduction satisfaction were closely related to the sensitivity of the TP (docetaxel plus cisplatin or carbopatin) regimen in ovarian cancer (P<0.05). These results demonstrated that CAFs highly secreted IL‑6 and promoted β‑TGF‑mediated EMT in ovarian cancer via the JAK2/STAT3 pathway, leading to inhibited apoptosis and subsequent paclitaxel resistance. Therefore, CAFs may be a new therapeutic target for the treatment of ovarian cancer.

Inflammation-based indicators such as neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), and platelet/lymphocyte ratio (PLR) have been reported to possess significant predictive value for several types of cancer. We investigated the predictive value of these 3 biomarkers on lymph node metastasis (LNM) and clinical outcome in patients with stage Ib1–IIa cervical cancer undergoing radical surgery. A total of 407 patients with FIGO stage Ib1–IIa cervical cancer, who underwent radical surgery between January 2006 and December 2009 at the Department of Gynecological and Oncology of Shandong Cancer Hospital Affiliated to Shandong University were recruited. Binary logistic regression analysis was performed to determine the relationship between PLR, NLR, dNLR, and LNM. Multivariate Cox regression analysis was performed to determine the association between the 3 indices and recurrence-free survival (RFS) and overall survival (OS). Optimal cut-off values for the 3 indices were determined by applying receiver operating curve (ROC) analysis. Univariate and binary logistic regression analyses both indicate that PLR was significantly associated with increased LNM (P < 0.05). In the multivariate survival analysis, increased preoperative PLR and NLR were significantly associated with reduced RFS (P = 0.001 and P = 0.002, respectively), whereas a combination of both PLR and NLR revealed a more significant association with reduced RFS (P < 0.001). Furthermore, increased preoperative PLR and NLR were significantly associated with reduced OS (P = 0.007 and P = 0.009, respectively), whereas the combined use of PLR and NLR revealed a more significant association with reduced OS (P = 0.003). PLR is an independent risk factor for increased LNM and clinical outcome in patients with stage Ib1–IIa cervical cancer. A combination of PLR and NLR may enable better risk stratification for predicting survival.

Background: Recently, pretreatment monocyte counts and the lymphocyte/monocyte ratio (LMR) have been proven to be significantly associated with the clinical outcomes of several types of cancer. In this study, we analyzed the prognostic significance of the LMR in stage Ib1–IIa cervical cancer patients who underwent a radical operation. Methods: A total of 485 patients with stage Ib1–IIa cervical cancer were included in this retrospective study. We evaluated the prognostic values of the absolute lymphocyte count, absolute monocyte count, and LMR by applying receiver operating characteristic curves. Kaplan–Meier curves and multivariate Cox proportional analyses were used to determine the recurrence-free survival (RFS) and overall survival (OS). Results: The area under the curve was 0.640 for the RFS and 0.647 for the OS using the LMR. In the univariate analysis, an elevated preoperative LMR was significantly associated with an increased RFS (hazard ratio [HR], 0.373; 95% confidence interval [CI]: 0.247–0.563; P<0.001), and this result remained significant in the multivariate analysis (HR, 0.439; 95% CI: 0.279–0.693; P<0.001). In the univariate analysis, an elevated LMR was also significantly associated with an increased OS (HR, 0.381; 95% CI: 0.233–0.622; P<0.001), and the significance persisted in the multivariate analysis (HR, 0.417; 95% CI: 0.244–0.714; P=0.001). Conclusion: A decreased pretreatment LMR is associated with a poor prognosis in stage Ib1–IIa cervical cancer patients who undergo a radical operation. A prospective study is warranted for further validation of our findings.

Aim: The study aimed to clarify the diagnostic value of exosomal miRNAs in epithelial ovarian cancer (EOC). Methods: Plasma exosomes were isolated from peripheral blood of EOC patients and healthy ... Plain language summary This study aimed to identify some miRNAs that can act as predictive and diagnostic markers of ovarian cancer (OC). To do this, miRNAs were isolated from blood samples of OC p...

Both circulating tumor cells (CTCs) and epithelial-mesenchymal transition (EMT) play an important role in invasion, migration and chemoresistant in tumor development. This study aimed to detect whether EMT occurred in human gastric CTCs and to explore the mechanism of EMT in human gastric CTCs. We analysed epithelial markers (pan-CK, E-cadherin), mesenchymal markers (N-cadherin, vimentin) EMT related miR‑200s, and Akt in gastric CTCs. The impact of miR‑200s on EMT, migration and invasion in CTCs was tested. We found that epithelial markers pan-CK, E-cadherin were decreased, and mesenchymal markers N-cadherin, vimentin were overexpressed in gastric CTCs. Expression of EMT related transcriptors, snail1, zeb1, twist1, were reversely correlated with miR‑200s, and were positively correlated with phospho-Akt. Upregulated of miR‑200s downregulated twist1 and zeb1 mRNA expression, and resulted in the supression of EMT, and impaired migration and invasion in gastric CTCs. Inhibition of p-Akt led to upregulation of miR‑200s. In conclusion, gastric CTCs exhibited remarkable EMT process, and p-Akt/miR‑200s signaling regulates EMT, migration and invasion in gastric CTCs.