No abstract

MicroRNAs, which serve as post-transcriptional modulators of numerous genes, have been found to be important regulators during the pathogenesis of osteosarcoma. This study demonstrates for the first time that microRNA-130a (miR-130a) is significantly upregulated in osteosarcoma, and associated with the metastasis of osteosarcoma. Elevated level of miR-130a was closely correlated with poor clinical features and prognosis of osteosarcoma patients. In vitro assays revealed that miR-130a could potentiate the migration, invasion and the epithelial-mesenchymal transtion (EMT) of osteosarcoma cells. Moreover, phosphatase and tensin homolog (PTEN) was confirmed as not only a direct downstream target but also a functional mediator of miR-130a. MiR-130a exerted promoting effects on metastatic behavior and EMT of osteosarcoma cells through suppressing PTEN expression. Based on these findings, we conclude that miR-130a is a promising prognostic biomarker for osteosarcoma patients, and targeting miR-130a may be a potential treatment option for osteosarcoma patients with metastasis.

The aims of this study were to discover if increased circulating microRNA-21 (miR-21) expression in serum is associated with lymph node metastasis in patients with cervical cancer and look further into the molecular mechanism of these. Whole-blood samples from 89 patients who have been histopathologically confirmed as having cervical cancer and 20 control subjects were collected, and then the association between lymph node metastasis and the level of circulating miR-21 was compared. Then cervical cancer cell lines HeLa (HPV-18 DNA, E6/E7RNA) and HT-3 (HPV DNA, E6/E7RNA) were used to confirm the interaction between miR-21 and RASA1. The role of RASA1 in cervical cancer cell migration was also studied in HeLa. Increased circulating miR-21 expression in serum is associated with lymph node metastasis in patients with cervical cancer. MicroRNA-21 reduces RASA1 expression in cervical cancer cell lines and promotes cervical cancer cell migration via RASA1. Furthermore, Ras-induced epithelial-mesenchymal transition contributes to miR-21/RASA1 axis promoting cervical cancer cell migration. Circulating miR-21 in serum could be a promising biomarker in auxiliary diagnosis of lymph node metastasis in cervical cancer, and inhibition of miR-21/RASA1 axis could be a possible strategy to restrain migration of cervical cancer.

Objective: To determine the predictive value of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer patients with surgical risk factors. Methods: Data of 662 cervical cancer patients (stages IB and IIA) with surgical risk factors treated at Zhejiang Cancer Hospital between 2008 and 2011 were retrospectively reviewed. Univariate log-rank test and multivariate Cox regression models were adopted to evaluate the relationship between 2018 FIGO stage and survival. Results: On re-staging of patients, 17.3%, 44.5%, 25.4%, and 37.1% of the patients with FIGO 2009 stage IB1, IB2, IIA1, and IIA2, respectively, were upgraded to FIGO 2018 IIIC1P stage, and 2.1%, 3.0%, 3.1%, and 2.1% patients, respectively, were upgraded to IIIC2P stage. The 5-year overall survival (OS) rates of patients with FIGO 2018 stage IB1, IB2, IB3, IIA1, IIA2, IIIC1P, and IIIC2P were 95.3%, 95.1%, 90.4%, 92.4%, 86.4%, 81.9%, and 56.3%, respectively. The 5-year progression-free survival (PFS) rates were 94.0%, 91.0%, 88.5%, 91.4%, 86.4%, 79.5%, and 43.8%, respectively. The 5-year OS rates of patients with 1–2 positive pelvic lymph nodes (PLNs) and those with >2 positive PLNs were 86.0% and 73.7%, respectively, and the 5-year PFS rates were 84.2% and 70.2%, respectively. OS and PFS of patients with 1–2 positive PLNs in stage IIIC1P were similar to those of patients in stage IIA2 without lymph node metastasis, but significantly better than those of patients with >2 positive PLNs. Multivariate analysis showed FIGO 2018 stage to be an independent prognostic factor for OS and PFS. Conclusion: The 2018 FIGO staging system for cervical cancer appears to be useful for predicting prognosis of patients with risk factors after radical surgery. Survival of stage IIA1 patients is better than that of stage IB3 patients. Stage IIIC1 is not homogenous; survival in stage IIIC1P depends on the number of positive PLNs.

Objective: To evaluate the factors associated with positive pelvic lymph nodes (LNs) on the survival of patients with 2018 FIGO stage IIIC1p cervical cancer. Methods: We retrospectively analyzed 155 patients with pelvic lymph node metastasis (LNM) confirmed by pathology after radical resection of cervical cancer treated at Zhejiang Cancer Hospital, China, between March 2008 and October 2011. We analyzed the influence of the factors associated with positive pelvic LNs on the survival of patients. Results: The 5-year progress-free survival (PFS) and overall survival (OS) of patients were 78.1% and 81.9%, respectively. The 5-year PFS and OS of patients with more than 2 LNM were worse compared with patients with 1 or 2 LNM (68.4% vs 83.7%, p =0.013; 72.4% vs 87.6%, p =0.017, respectively). The 5-year PFS and OS of patients with more than 2 LNM sites were worse than that of patients with 1 or 2 LNM sites (60.0% vs 82.4%, p =0.008; 70.0% vs 84.8%, p =0.045, respectively). The 5-year PFS and OS of patients with common iliac LNM was poorer than that of patients without common iliac LNM (60.7% vs 81.9%, p =0.008; 67.9% vs 85.0%, p =0.020, respectively). Compared with other patients, the survival of patients with these three factors (more than 2 LNM, more than 2 LNM sites, and common iliac LNM) was the worst ( p <0.05). Conclusion: More than 2 LNM, more than 2 LNM sites, and common iliac LNM were predictive factors of poor survival in stage IIIC1p cervical cancer patients. Survival of patients with stage IIIC1p cervical cancer declined with increasing presence of such factors. The combined evaluation of the factors associated with positive pelvic LNs is a more comprehensive and pragmatic approach in evaluating the prognosis of cervical cancer.

Background and purposeHow to protect the ovarian function during radiotherapy is uncertain. The purpose of this study was to explore the association between the location of the transposed ovary and the ovarian dose in patients with cervical cancer received radical hysterectomy, ovarian transposition, and postoperative pelvic radiotherapy.MethodsA retrospective analysis was conducted of 150 young patients with cervical cancer who received radical hysterectomy, intraoperative ovarian transposition, and postoperative adjuvant radiotherapy in Zhejiang Cancer Hospital. Association between location of the transposed ovaries and ovarian dose was evaluated. The transposed position of ovaries with a satisfactory dose was explored using a receiver operator characteristic curve (ROC) analysis. Patients’ ovarian function was followed up 3 months and 1 year after radiotherapy.ResultsA total of 32/214 (15%) transposed ovaries were higher than the upper boundary of the planning target volume (PTV). The optimum cutoff value of > 1.12 cm above the iliac crest plane was significantly associated with ovaries above the upper PTV boundary. When the ovaries were below the upper boundary of PTV, the optimum cutoff value of transverse distance > 3.265 cm between the ovary and PTV was significantly associated with ovarian max dose (Dmax) ≤ 4Gy, and the optimum cutoff value of transverse distance > 2.391 cm was significantly associated with ovarian Dmax≤5Gy. A total of 77 patients had received complete follow-up, and 56 patients (72.7%) showed preserved ovarian function 1 year after radiotherapy, which was significantly increased compared with 3 months (44.2%) after radiotherapy.ConclusionsThe location of transposed ovaries in patients with cervical cancer is significantly correlated with ovarian dose in adjuvant radiotherapy. We recommend transposition of ovaries > 1.12 cm higher than the iliac crest plane to obtain ovarian location above PTV. When the transposed ovary is below the upper boundary of PTV, ovarian Dmax ≤4Gy may be obtained when the transverse distance between the ovary and PTV was > 3.265 cm, and the ovarian Dmax≤5Gy may be obtained when the transverse distance was > 2.391 cm.

Background: Whether metastasectomy improves prognosis of gastric cancer patients with ovarian metastases (Krukenberg tumors) is not clear. In this study, we examined the survival benefit of metastasectomy combined with chemotherapy for treatment of synchronous Krukenberg tumors from gastric cancer and identified the prognostic factors.Methods: The subjects of this study were patients diagnosed as synchronous Krukenberg tumors of gastric origin in the period between December 2004 and December 2015. Patients were classified in accordance with treatment modality: metastasectomy group (metastasectomy combined with chemotherapy) and non-metastasectomy group (chemotherapy alone). Clinicopathological characteristics together with treatment records were investigated in detail and their relationship with survival outcomes was examined.Results: Out of a total of 103 patients, 54 (52.4%) underwent metastasectomy of Krukenberg tumors while 49 (47.6%) patients had chemotherapy alone. Overall survival (OS) in the metastasectomy group was significantly longer than that in the non-metastasectomy group (18.9 months vs. 12.4 months, respectively; P<0.001). Metastasectomy (hazard ratio [HR] 0.486; 95% confidence interval [CI] 0.323-0.729; P<0.001), signet ring cells (HR 1.938; 95% CI 1.182-3.175; P=0.009), peritoneal carcinomatosis (HR 1.934; 95% CI 1.230-3.049; P=0.004), expression of estrogen receptor-β (ER-β) (HR 0.404; 95% CI 0.251-0.648; P<0.001), and progesterone receptor (PR) (HR 0.496; 95% CI 0.301-0.817; P<0.001) were independent predictors of OS.Conclusion: Metastasectomy combined with chemotherapy showed an association with survival benefit in patients with synchronous Krukenberg tumors from gastric cancer. Metastasectomy, expression of ER-β and PR, peritoneal carcinomatosis, and signet ring cells were independent predictors of survival. Further prospective studies are warranted.

Objective This study aimed to investigate the clinical and histological features affecting the survival of patients with early cervical squamous cell cancer treated with radical hysterectomy. Methods We retrospectively analyzed clinical and histological data for patients with stage IB-IIA cervical cancer treated by radical hysterectomy at Zhejiang Cancer Hospital from August 2008 to January 2013. Results A total of 1435 patients were included in the study. Cox regression analysis identified tumor size >4 cm, lymphovascular space involvement (LVSI), lymph node ratio (LNR), and squamous cell carcinoma antigen (SCC-Ag) >2.65 ng/mL as independent prognostic risk factors. Among 1096 patients without high pathological risk factors, the 5-year local recurrence rates for SCC-Ag ≤2.65 and >2.65 ng/mL were 6.6% and 25.7%, respectively. Among 332 patients with lymph node positivity, the overall survival rates for LNR ≤0.19 and >0.19 were 87.8% and 55.6%, respectively. Conclusions LVSI, tumor size >4 cm, LNR >0.19, and SCC-Ag >2.65 ng/mL may predict a poor prognosis in patients with early cervical squamous cell cancer treated with radical hysterectomy. SCC-Ag >2.65 ng/mL may be a useful prognostic factor guiding the use of postoperative radiotherapy in patients without pathologic risk factors.