Establishment of a Prognostic Nomogram for Cancer-Specific Survival in Patients With Base-of-Tongue Squamous Cell Carcinoma: A Retrospective Study Based on the SEER Database.

BACKGROUND: The aim of this retrospective study was to construct and clinically apply a nomogram for cancer-specific survival (CSS) in patients diagnosed with base-of-tongue squamous cell carcinoma (BOTSCC) to predict their survival prognosis. METHODS: We collected 8448 patients diagnosed with BOTSCC during 2004-2015 from the Surveillance, Epidemiology, and End Results (SEER) database and divided 30% and 70% of them into validation and training cohorts, respectively. We utilized backward stepwise regression in the Cox model to select variables. Predictive variables were subsequently identified from the variables selected above by using multivariate Cox regression. The new survival model was compared with the American Joint Committee on Cancer (AJCC) prognosis model using the following variables: calibration curve, time-dependent area under the receiver operating characteristic curve (AUC), concordance index (C-index), integrated discrimination improvement (IDI), decision-curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: A nomogram was established for predicting the CSS probability in patients with BOTSCC. Factors including sex, race, age at diagnosis, marital status, radiotherapy status, chemotherapy status, TNM AJCC stage, surgery status, tumor size, and months from diagnosis to treatment were selected through multivariate Cox regression as independent predictors of CSS. Calibration plots indicated that the model we established had satisfactory calibration ability. The AUC, C-index, IDI, DCA, and NRI results illustrated that the nomogram performed explicit prognoses more accurately than did the AJCC system alone. CONCLUSION: We identified the relevant factors affecting the survival of BOTSCC patients and analyzed the data on patients suffering from BOTSCC in the SEER database. These factors were used to construct a new nomogram to give clinical staff a more-visual prediction model for the 3-, 5-, and 8-year probabilities of CSS for patients newly diagnosed with BOTSCC, thereby aiding clinical decision making.

The impact of prenatal use of oral Clostridium butyricum on maternal group B Streptococcus colonization: A retrospective study.

OBJECTIVE: The aim of this study is to examine the effect of taking Clostridium butyricum (Miyarisan BM) orally for 4 weeks since the 32+0 weeks of gestation on preventing Group B Streptococcus colonization. MATERIALS AND METHODS: We retrospectively collected data on the pregnancy outcomes of 1602 women between October 2017 and August 2019. The control group received standard antenatal care, and the intervention group received standard antenatal care with a daily oral dose of probiotics since the 32+0 weeks of gestation. The daily dose was one pack of C. butyricum (Miyarisan BM) once or twice a day. A vaginal Group B Streptococcus swab was collected between 36+0 and 36+6 weeks of gestation. RESULTS: After applying the designated exclusion criteria, the total number of participants was 1576. The Group B Streptococcus colonization rate was significantly decreased in the intervention group (P = 0.0338; adjusted OR: 0.66 (0.45-0.97)). CONCLUSION: Probiotics can reduce the colonization rate of Group B Streptococcus in the vagina and rectum under three conditions: (1) intervention of adequate length, (2) sufficient probiotic dose, and (3) effective probiotics.

Author Correction: The role of sentrin-specific protease 2 substrate recognition in TGF-ß-induced tumorigenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Meta-Analysis Results on the Association Between TP53 Codon 72 Polymorphism With the Susceptibility to Oral Cancer.

Objectives: TP53 is an important tumor suppressor gene to maintain genomic integrity, and its mutations increase the susceptibility to oral carcinoma. Previous published studies have reported the relation of TP53 codon 72 polymorphism with the risk of oral carcinoma, but the results remain controversial and inconclusive. Methods: We therefore utilized meta-analysis based on a comprehensive search in PubMed, EMBASE, and Google of Scholar databases up to August 19, 2017. Results: Total 3,525 cases and 3,712 controls from 21 case-control studies were selected. We found no significant association between TP53 codon 72 polymorphism and oral carcinoma susceptibility in all genetic contrast models, including subgroup analysis based on control source and ethnicity. Furthermore, TP53 codon 72 polymorphism was not significant associated with oral carcinoma susceptibility in tobacco or alcohol use, and HPV infection status. Our results were confirmed by sensitivity analysis and no publication bias was found. Conclusions: Taken together, our data indicate that TP53 codon 72 polymorphism is not associated with the susceptibility to oral carcinoma.

The role of sentrin-specific protease 2 substrate recognition in TGF-ß-induced tumorigenesis.

Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-ß signals into the nuclei. Although many cellular factors are involved in TGF-ß induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-ß. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-ß repression. The SENP2363~400 segment is critical for TGF-ß-induced cell migration, which is correlated with SENP2363~400 deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-ß induced cancer cell migration.

SUMOylation of XRCC1 activated by poly (ADP-ribosyl)ation regulates DNA repair.

XRCC1 is an essential scaffold protein for base excision repair (BER) and helps to maintain genomic stability. XRCC1 has been indicated as a substrate for small ubiquitin-like modifier modification (SUMOylation); however, how XRCC1 SUMOylation is regulated in cells and how SUMOylated XRCC1 regulates BER activity are not well understood. Here, we show that SUMOylation of XRCC1 is regulated in cells under methyl-methanesulfonate (MMS) treatment and facilitates BER. Poly(ADP-ribose) polymerase 1 (PARP1) is activated by MMS immediately and synthesizes poly(ADP-ribose) (PAR), which in turn promotes recruitment of SUMO E3 TOPORS to XRCC1 and facilitates XRCC1 SUMOylation. A SUMOylation-defective mutant of XRCC1 had lower binding activity for DNA polymerase beta (POLB) and was linked to a lower capacity for repair of MMS-induced DNA damages. Our study therefore identified a pathway in which DNA damage-induced poly(ADP-ribosyl)ation (PARylation) promotes SUMOylation of XRCC1, which leads to more efficient recruitment of POLB to complete BER.

Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A Meta-Analysis.

Background. Previous studies have revealed that gene polymorphisms of inflammatory factors may influence the development or progression of periodontitis, a main cause of tooth loss in adults; however, due to limitations of individual studies, inconsistent findings were reported. Objective. To meta-analytically investigate the relationship between periodontitis and the Interleukin-4 (IL-4) and Interleukin-4 receptor (IL-4R) gene polymorphisms. Methods. Databases were searched for relevant case-control studies. After study selection based on the predefined selection criteria, methodological quality assessment and data extraction were conducted independently by two reviewers, before subsequent statistical analyses. Results. 37 studies involving 4,385 patients and 5,168 controls were included. All the studied IL-4 polymorphisms were not significantly associated with periodontitis, except the -33C/T (CT versus CC: OR = 0.50, 95% CI = 0.28-0.88) associated with reduced AgP susceptibility. Positive association was found between IL-4R Q551 polymorphism and periodontitis susceptibility in three genetic models (R versus Q: OR = 1.59, 95% CI = 1.14-2.22; QR versus QQ: OR = 1.84, 95% CI = 1.21-2.80; RR + QR versus QQ: OR = 1.82, 95% CI = 1.22-2.72). Conclusions. A positive association exists between the IL-4R Q551R polymorphism and occurrence of CP. The IL-4 -33 CT genotype is negatively associated with the occurrence of AgP.

HIC1 interacts with and modulates the activity of STAT3.

HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene, expression of which is frequently suppressed in human cancers. Very little is known about the molecular basis of HIC1 in antagonizing oncogenic pathways. Here, we report that HIC1 forms complexes with the signal transducers and activators of transcription 3 (STAT3) and attenuates STAT3-mediated transcription. STAT3 was identified as a HIC1-interacting protein by affinity capture and followed by mass spectrometry analysis. Overexpression or depletion of HIC1 resulted in decreased or increased levels of interleukin-6 (IL-6)/oncostatin M (OSM)-induced STAT3-mediated reporter activity and expression of target genes such as VEGF and c-Myc, respectively. Furthermore, HIC1 suppressing the VEGF and c-Myc promoter activity and the colony formation of MDA-MB 231 cells were STAT3-dependent. Further studies showed that HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. Domain mapping study revealed that HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells. Altogether, our findings not only provide a novel role of HIC1 in antagonizing STAT3-mediated activation of VEGF and c-Myc gene expression and cell growth, but also elucidate a molecular basis underlying the inhibitory effect of HIC1 on STAT3 transcriptional potential.

Cdh1 controls the stability of TACC3.

Transforming acidic coiled-coil protein 3 (TACC3) was reported to be important for regulating mitotic spindle assembly and chromosome segregation. While the protein level of TACC3 was shown to be altered during cell cycle progression, the molecular mechanism in controlling TACC3 level is unclear. Here, we show that TACC3 protein level can be regulated by Cdh1, a well known activator of anaphase-promoting complex/cyclosome. We identified Cdh1 as an interacting partner of TACC3 by a yeast array screen. Both in vitro and in vivo binding studies indicated that TACC3 can form complexes with Cdh1. Depletion of endogenous Cdh1 prolonged TACC3 protein level during mitotic exit. Alteration of Cdh1 level by ectopic overexpression or siRNA knockdown correlated well with an increase or decrease of ubiquitinated TACC3, respectively. Furthermore, the domain mapping studies of TACC3 revealed that multiple domains are involved in Cdh1-regulated degradation of TACC3. Altogether, our findings suggest that Cdh1 controls TACC3 protein stability during mitotic exit.