Objective: Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC. Methods: PubMed, Embase, ClinicalTrials.gov, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords "ovarian cancer/neoplasms", "primary debulking surgery", and "neoadjuvant chemotherapy". Results: The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13-1.49; heterogeneity: p<0.001, I 2 =82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32-2.17; heterogeneity: p<0.001, I 2 =81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06-0.51; heterogeneity: p=0.698, I 2 =0%) and major infection (RR=0.29, 95% CI=0.17-0.51; heterogeneity: p=0.777, I 2 =0%) compared with patients administered PDS. Conclusions: This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients.
Asparaginase like 1 (ASRGL1) protein belongs to the N-terminal nucleophile group, cleaving the isoaspartyl-dipeptides and L-asparagine by adding water. It tends to be overexpressed in cancerous tumors including ovarian cancer and breast tumors. The present study assessed the potential ability of ASRGL1 as a molecular target in gene-based cervical cancer treatment. The protein expression level of ASRGL1 was determined in paraffin-embedded tumor specimen by immunohistochemistry. Additionally, in order to assess the activity of ASRGL1 during the process of cervical cancer cell multiplication, ASRGL1-short hairpin (sh) RNA-expressing lentivirus was established, which was used to infect SiHa cells. The Cellomics ArrayScan VT1 Reader identified the influence of downregulation on SiHa caused by RNA interference-intervened ASRGL1. Flow cytometric analysis was also performed to evaluate the influence. The cyclin dependent kinase (CDK2), cyclin A2, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) expression levels were assessed by western blot analysis. ASRGL1 was observed to be overexpressed in cervical cancer tissues when compared with the adjacent normal tissues. The knockdown of ASRGL1 in SiHa by ASRGL1-shRNA lentivirus infection significantly inhibited cell growth and enhanced cellular apoptosis; the cells were also captured during the S phase. The knockdown of ASRGL1 expression led to the increased expression of Bax and decreased expression of Bcl-2, CDK2 and cyclin A2. In conclusion, ASRGL1 was closely associated with growth and apoptosis in cervical cancer. Therefore, ASRGL1 may be a novel, potentially effective anti-cervical cancer therapy.
Background Cervical cancer ranks second among malignancies in females around the world. Due to the elevated incidence and mortality of this malignancy, deciphering its pathogenesis and identifying related biomarkers is urgently required. Methods First, raw cervical squamous cell carcinoma (CESC) data in GSE63514 were downloaded from the Gene Expression Omnibus (GEO) database. Then, weighted Correlation Network Analysis (WGCNA) was performed to build a co-expression network. Next, comprehensive bioinformatics was performed to determine hub genes, and assess the associated functional annotation, prognostic signature, tumor immunity, DNA mismatch repair, methylation mechanism, candidate molecular drugs, and gene mutations. Results From the key module, ALOX12B, KRT78, RHOD and ZNF750 were selected for validation. K-M plots indicated that these genes had good diagnostic and prognostic values in CESC. Moreover, mutations in these hub genes resulted in the downregulation of most immune genes in CESC. On the other hand, most of the four core genes were negatively correlated with DNA mismatch genes. In addition, we found that RHOD and ZNF750 had decreased methylation in the disease state, while ALOX12B and KRT78 showed no significant differences. Meanwhile, GSVA revealed that most core genes had associations with P53 signaling and the hypoxia signaling pathway. Conclusion WGCNA could identify groups of genes significantly associated with cervical cancer prognosis. These findings provide new insights into CESC pathogenesis, and identify ALOX12B, KRT78, RHOD and ZNF750 as candidate biomarkers for CESC diagnosis and prognosis.
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