Yuebo Yang

Significance of Gelsolin Superfamily Genes in Diagnosis, Prognosis and Immune Microenvironment Regulation for Endometrial Cancer

ABSTRACTBackgroundPreviously, anti‐CTLA4 and anti‐PD‐1/PD‐L1 immunotherapies have shown limited efficacy in MSI‐H/MMR‐D endometrial cancer, leading to poor clinical outcomes. The gelsolin superfamily, which includes GSN, SCIN, VILL, VIL1, CAPG, AVIL, SVIL, and FLII, plays crucial roles in cell motility and gene regulation.AimsThe objective of this study is to explore the potential therapeutic and prognostic implications of the gelsolin superfamily in EC.Materials & MethodsData from TCGA, GEPIA, THPA, UALCAN, and Kaplan–Meier plotter databases were analyzed to investigate the expression and clinical relevance of gelsolin superfamily members. Co‐expression networks of the gelsolin superfamily were assessed using LinkedOmics, GeneMANIA, and NetworkAnalyst. The relationship between gelsolin superfamily and immune cell infiltration was investigated using TIMER, ImmuCellAI, and GEPIA.ResultsWe found that high expressions of CAPG, AVIL, and SVIL were associated with poor prognosis, while high expressions of GSN and FLII were linked to better outcomes in EC. Functional enrichment analysis indicated the involvement of gelsolin superfamily members in pathways related to estrogen response, MYC targets, epithelial–mesenchymal transition, TGF beta signaling, MTORC1 signaling, oxidative phosphorylation, inflammatory response, and IL6‐JAK‐STAT3 signaling. Furthermore, gelsolin superfamily members demonstrated strong correlations with the levels of monocytes, natural killer T, naive CD4+ T, follicular helper T, and central memory T in EC. In vitro studies showed that silencing CAPG and FLII could inhibit proliferation and metastasis in endometrial cancer cell lines.ConclusionThese findings indicate the significant association of gelsolin superfamily members with prognosis and immunological status in endometrial cancer.

Recurrence‐Associated Multi‐RNA Signature to Predict Disease‐Free Survival for Ovarian Cancer Patients

Ovarian cancer (OvCa) is an intractable gynecological malignancy due to the high recurrence rate. Several molecular biomarkers have been previously screened for early identifying patients with a high recurrence risk and poor prognosis. However, all the known studies focused on a single type of RNAs, not integrating various types. This study was to construct a new multi‐RNA‐based model to predict the recurrence and prognosis for OvCa patients by using the messenger RNA (mRNA, including long noncoding RNA (lncRNA)) and microRNA (miRNA) sequencing data of The Cancer Genome Atlas database. After univariate Cox regression and least absolute shrinkage and selection operator analyses, a multi‐RNA‐based signature (2 miRNAs: hsa‐miR‐508, hsa‐miR‐506; 1 lncRNA: TM4SF1‐AS1; 11 mRNAs: MAGI3, SLAMF7, GLI2, PDK1, ARID3A, PLEKHG4B, TNFAIP8L3, C1QTNF3, NDUFAF1, CH25H, TMEM129) was generated and used to establish a risk score model. The high‐ and low‐risk patients classified by the median risk score exhibited significantly different recurrence risks (89% versus 61%, p < 0.001) and survival time (the area under the receiver operating characteristic curve (AUC) = 0.901 for 5‐year disease‐free survival (DFS)). This risk model was independent of other clinical features and superior to pathologic staging for DFS prediction (AUC, 0.906 versus 0.524; C‐index, 0.633 versus 0.510). Furthermore, some new interaction axes were revealed to explain the possible functions of these RNAs (competing endogenous RNA: TM4SF1‐AS1‐miR‐186‐STEAP2, LINC00536‐miR‐508‐STEAP2, LINC00475‐miR‐506‐TMEM129; coexpression: LINC00598‐PLEKHG4B). In conclusion, this multi‐RNA‐based risk model may be clinically useful to stratify OvCa patients with different recurrence risks and survival outcomes and included RNAs may be potential therapeutic targets.

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy (with or without Chemotherapy) in Patients with Stage IB2, IIA, or IIB Cervical Cancer: A Systematic Review and Meta-Analysis

Background. This study was to compare the efficacy and safety between neoadjuvant chemotherapy followed by radical surgery (NACT+RS) and radiotherapy only (RT) or concurrent chemoradiotherapy (CCRT) for treatment of patients with stage IB2, IIA, or IIB cervical cancer. Method. The electronic databases of PubMed, Embase, and the Cochrane Library were searched to screen relevant studies from their inception to October 2018. Clinical data including overall survival (OS), disease-free survival (DFS), and adverse events were extracted. Egger’s test was used to evaluate the publication bias, and sensitivity analysis was conducted to estimate the robustness of results. Results. Finally, three randomized controlled trials (RCTs) and two case-control studies consisting of 1,275 patients with stage IB2, IIA, or IIB cervical cancer were included in the current study. Overall, pooled results showed no significant differences in OS ((hazard ratio HR=0.603, 95%CI=0.350−1.038) and DFS (HR=0.678, 95%CI=0.242−1.904) for patients treated with NACT+RS compared with RT only or CCRT, but the subgroup analysis showed that the OS and DFS were significantly longer in the NACT+RS groups than the RT or CCRT group (OS: HR=0.431, 95%CI=0.238−0.781, p=0.006; DFS: HR=0.300, 95%CI=0.187−0.482, p<0.001) for the population with median follow-up time of more than 60 months. For adverse events, the incidence of thrombocytopenia in the NACT+RS group was significantly higher than that in the RT only or CCRT group (relative risk RR=3.240, 95% CI 1.575-6.662), while the incidence of diarrhea was significantly lower than that in the RT only or CCRT group (RR=0.452, 95% CI =0.230-0.890). Conclusion. These findings suggest that the short-term therapeutic effects of the two treatments may be possibly equal for patients with stage IB2-IIB cervical cancer, but the long-term effects for improving OS and DFS may be better using NACT+RS compared with the RT only or CCRT.