Corrigendum: DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

[This corrects the article DOI: 10.3389/fonc.2021.629974.].

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

Nomograms to Predict the Density of Tumor-Infiltrating Lymphocytes in Patients With High-Grade Serous Ovarian Cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have important roles in predicting tumor therapeutic responses and progression, however, the method of evaluating TILs is complicated. We attempted to explore the association of TILs with clinicopathological characteristics and blood indicators, and to develop nomograms to predict the density of TILs in patients with high-grade serous ovarian cancer (HGSOC). METHODS: The clinical profiles of 197 consecutive postoperative HGSOC patients were retrospectively analyzed. Tumor tissues and matched normal fallopian tubes were immunostained for CD3+, CD8+, and CD4+ T cells on corresponding tissue microarrays and the numbers of TILs were counted using the NIH ImageJ software. The patients were classified into low- or high-density groups for each marker (CD3, CD4, CD8). The associations of the investigated TILs to clinicopathological characteristics and blood indicators were assessed and the related predictors for densities of TILs were used to develop nomograms; which were then further evaluated using the C-index, receiver operating characteristic (ROC) curves and calibration plots. RESULTS: Menopausal status, estrogen receptor (ER), Ki-67 index, white blood cell (WBC), platelets (PLT), lactate dehydrogenase (LDH), and carbohydrate antigen 153 (CA153) had significant association with densities of tumor-infiltrating CD3+, CD8+, or CD4+ T cells. The calibration curves of the CD3+ (C-index = 0.748), CD8+ (C-index = 0.683) and CD4+ TILs nomogram (C-index = 0.759) demonstrated excellent agreement between predictions and actual observations. ROC curves of internal validation indicated good discrimination for the CD8+ TILs nomogram [area under the curve (AUC) = 0.659, 95% CI 0.582-0.736] and encouraging performance for the CD3+ (AUC= 0.708, 95% CI 0.636-0.781) and CD4+ TILs nomogram (AUC = 0.730, 95% CI 0.659-0.801). CONCLUSION: Menopausal status, ER, Ki-67 index, WBC, PLT, LDH, and CA153 could reflect the densities of T cells in the tumor microenvironment. Novel nomograms are conducive to monitor the immune status of patients with HGSOC and help doctors to formulate the appropriate treatment strategies.

Impact of nonspecific death on overall survival in early-stage epithelial ovarian cancer patients.

OBJECTIVE: To estimate the impacts of nonovarian cancer-specific death (non-OCSD) and ovarian cancer-specific death (OCSD) on early-stage patients, and to determine which statistical method yielded survival results most similar to real-world situations. METHODS: Data of patients with early-stage epithelial ovarian cancer from 1988 to 2015 registered in the Surveillance, Epidemiology, and End Results database were analyzed. The primary outcome events of epithelial ovarian cancer were OCSD, non-OCSD, or alive. Incidences of non-OCSD and OCSD with different clinicopathological factors, cumulative incidences of non-OCSD and OCSD, and overall survival impact of non-OCSD were analyzed. RESULTS: A total of 1606 non-OCSD (8.9%) and 3022 OCSDs (16.8%) were analyzed. Several independent features were associated with non-OCSD, including age (>60 years), radiotherapy, and marital status. In patients with histology (eg, endometrioid or mucinous), well-differentiated cells, stage I disease, or widowed marital status, as well as age older than 60, non-OCSD rates of all causes of death notably distorted overall survival, resulting in inaccurate and biased interpretations. CONCLUSIONS: Overall survival was greatly influenced by non-OCSD in early epithelial ovarian cancer. Future clinical trials should consider non-OCSD as a competing risk event, especially among patients older than 60 years and those with well-differentiated cells, no chemotherapy, and widowed marital status.

miR­96 exerts an oncogenic role in the progression of cervical cancer by targeting CAV­1.

Cervical cancer is the 4th most common malignant tumor type affecting women worldwide; however, its molecular mechanisms are not fully understood. Previous studies have indicated that microRNAs (miRs) serve crucial roles in the cellular functions of tumors. miR­96 is involved in the tumorigenesis of many cancer types. The aim of the present study was to investigate the role and mechanism of miR­96 in the progression of cervical cancer. The present results suggested that overexpression of miR­96 significantly enhanced the proliferative, migratory and invasive abilities of cervical cancer cells, while inhibiting miR­96 had the opposite effects. Additionally, activation of the Akt/mTOR signaling pathway was enhanced by miR­96 overexpression, while it was inhibited by the miR­96 inhibitor. Moreover, it was identified that miR­96 may directly target caveolin­1 (CAV­1) to decrease its expression level. Furthermore, overexpression of CAV­1 could reverse the increase in cell proliferation, migration and invasion induced by miR­96, as well as the upregulation of the Akt/mTOR signaling pathway. In conclusion, the present results suggested that miR­96 may have an oncogenic role in the progression of cervical cancer by targeting CAV­1. Therefore, miR­96 may be a potential target for cervical cancer therapy.