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Abstract
ObjectiveTo clarify the clinical relevance of WASP like actin nucleation promoting factor (WASL) in patients with cervical cancer and associated mechanisms.Methods and MaterialsWe obtained high prediction accuracy and determined the correlation between the expression of WASL and the clinical characteristics of cervical cancer patients. Differentially expressed genes (DEGs) were identified using microarray. Gene ontology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were performed to determine potentially relevant mechanisms related to the prognostication ability of WASL expression.ResultsChi-square test and multivariable logistic regression analysis suggested that lower expression of WASL was associated with lower pathological stage (chi-square test: p = 0.022, chi-square = 9.613; logistic regression: OR = 0.869, 95% CI: 0.756–0.991, p = 0.041). Patients in the WASL high expression group have worse overall survival (OS) [hazard ratio (HR): 0.555, 95% CI: 0.348–0.884, log-rank p = 0.012] and recurrence-free survival (RFS) (HR = 0.449, 95% CI: 0.215–0.934, log-rank p = 0.028) compared with those in the WASL low expression group. Univariate and multivariable Cox proportional hazards regression model suggested that WASL expression was an independent prognostic factor for predicting OS and RFS in cervical cancer. DEGs were mostly enriched GO terms related to DNA replication or the proliferation of tumor cells. The results of GSEA suggested samples in the WASL knockdown group were enriched in glycolysis, TNF-α signaling via NFkB, mTORC1 signaling, and Wnt/β-catenin signaling.ConclusionsWASL expression was associated with the pathological stage, and it might be an independent prognostication factor in patients with cervical cancer. Knockdown of WASL might be correlated with biological processes such as glycolysis, TNFα signaling, mTOR signaling, and Wnt/β-catenin signaling.
Highlights
Cervical cancer represents one of the most frequent malignancies in the female reproductive system (Small et al, 2017)
The expression values of the cervical cancer samples were in log2 (x + 1) transformed RNA-Seq by expectationmaximization (RSEM) normalized count
A total of 290 patients with cervical cancer in The Cancer Genome Atlas (TCGA)-CESC were included in this study, of which 149 patients were younger than or were 50 years old, and 141 patients were older than 50 years
Summary
Cervical cancer represents one of the most frequent malignancies in the female reproductive system (Small et al, 2017). For patients with early cervical cancer (carcinoma in situ, stages 1 and 2 cervical cancer), surgery to remove the tumor, the cervix, and some or all of the womb (conization, hysterectomy with or without bilateral salpingo-oophorectomy, radical trachelectomy) or radiotherapy (internal radiation therapy, radiation therapy with or without chemotherapy) or a combination of both is often recommended. For patients with advanced cervical cancer, radiation therapy as palliative therapy to relieve symptoms with or without chemotherapy, targeted therapy, and surgery to remove pelvic lymph nodes are often recommended (Li et al, 2016; Hu and Ma, 2018). Despite continuous improvements in surgical techniques, radiotherapy equipment, etc., the therapeutic effect on patients with cervical cancer has not improved fundamentally in the past 40 years. The overall 5year survival rate of cervical cancer patients is about 40%, and it sharply decreases to about 16.5% for patients with advanced or metastatic cervical cancer (Mapanga et al, 2018; Alimena et al, 2019)
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