Significant association between IL-18 and OCT4 gene polymorphisms in susceptibility and clinical characteristics of prostate cancer

Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 gene polymorphisms are associated with prostate cancer remain unclear. In this study, we aimed to determine whether the presence of IL-18 and OCT4 polymorphisms were associated with size, grade, tumor, nodes and metastasis(TNM) stage, or survival in patients with prostate cancer.Methods Polymorphisms in OCT4 and IL-18 genes were evaluated to determine susceptibility to prostate cancer in 120 patients. A control group consisted of 125 Chinese participants. Genotyping was performed using TaqMan allelic discrimination assays, and statistical analysis was performed using SPSS. Results No association was found between OCT4 and IL-18 gene polymorphisms and prostate cancer susceptibility. For OCT4 AA and IL-18-607 CC genotypes, there was a significant association with higher tumor grade(P = 0.03 and P = 0.025) and stage(P = 0.04 and P = 0.001). The OCT4 and IL-18-137 GG genotype was correlated with higher tumor grade(P = 0.028) and stage(P = 0.008). Furthermore, OCT4 AA was significantly more frequent in patients with lymph node metastasis(P = 0.02) and distant metastasis(P = 0.01). The Cox proportional hazard model showed that tumor grade and stage grouping were independent prognostic factors but IL-18 and OCT4 polymorphisms were not. Conclusion The OCT4 gene may have a profound effect on prostate cancer risk. Polymorphism variants in the IL-18(IL-18-607 and IL-18-137) and OCT4 genes may be associated with poor prognoses for individuals with prostate cancer.

Methylation profile of bovine Oct4 gene coding region in relation to three germ layers

Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues（heart, liver, lung, cerebrum and cerebellum） from three germ layers were chosen from low age（50–60 d） and advanced age（60–70 d） of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different（P〈0.01） between any two of three germ layers in low age（〈60 d）, but kept steady of advanced age（P〉0.05）（〉60 d）, suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm（cerebrum and cerebellum）, there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age（P〉0.05）, but the result of endoderm（liver and lung） and mesoderm（heart） were on the contrary（P〈0.01）, which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th Cp G-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers（P〈0.05）, indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming.

OCT4’s role and mechanism underlying oral squamous cell carcinoma

Oral squamous cell carcinoma(OSCC),a common malignancy of the head and neck,ranks sixth worldwide in terms of cancers with the most negative impact,owing to tumor relapse rates,cervical lymphnode metastasis,and the lack of an efficacious systemic therapy.Its prognosis is poor,and its mortality rate is high.Octamer-binding transcription factor 4(OCT4)is a member of the Pit-Oct-Unc(POU)family and is a key reprogramming factor that produces a marked effect in preserving the pluripotency and self-renewal state of embryonic stem cells(ESCs).According to recent studies,OCT4 participates in retaining the survival of OSCC cancer stem cells(CSCs),which has far-reaching implications for the occurrence,recurrence,metastasis,and prognosis of oral carcinogenesis.Therefore,we summarize the structure,subtypes,and function of OCT4 as well as its role in the occurrence,progression,and prognosis of OSCC.

Leukemia Inhibitory Factor Enhanced the Developmental and Implantation Compatibility of Mouse Embryos in Co-culture with Human Endometrial Epithelial Cells

Objective:Among the variousin vitro embryo culture systems,co-culture has demonstrated remarkable effects in pre-implantation embryo development owing to the production of embryo-nourishing factors.Nevertheless,little is known about the secretion of these factors.Therefore,in this study,the effect of leukemia inhibitory factor(LIF),one of the most important nourishing factors in the early development of mouse embryos,in human endometrial epithelial cells(hEECs)was evaluated.Methods:Two-cell stage embryos were collected from the oviducts of hyper-stimulated and mated mice and cultivated in a co-culture with an hEEC monolayer with or without LIF.The quality and developmental and attachment potential rates of cultured embryos were evaluated by determining the levels of octamer-binding transcription factor 4(Oct4)and caudal type homeobox 2(Cdx2)transcripts.Results:LIF significantly increased the developmental rate(82.67%vs.61.04%,respectively)and attachment rate(64%vs.45.45%,respectively)of mouse embryos co-cultured with hEECs compared to those in untreated embryos.The expression levels ofOct4 andCdx2 in blastocysts cultured in the presence of LIF were higher than those in blastocysts cultured without LIF.Conclusions:Despite the secretion of LIF by hEECs during co-culture with embryos,the amount of this factor was insufficient,and its addition to the culture media could increase the developmental potential of embryos.

Mutational Analysis of OCT4+ and OCT4− Circulating Tumour Cells by Single Cell Whole Exome Sequencing in Stage I Non-Small Cell Lung Cancer Patients

Circulating tumour cells(CTCs)were enriched in the peripheral blood of four patients with Stage I non-small cell lung cancer(NSCLC).Octamer-binding transcription factor-4 positive(OCT4+)and negative(OCT4−)CTCs were identified and captured by interphase fluorescence in situ hybridisation(iFISH).Single cell whole exome sequencing(WES)was performed and the corresponding bioinformatics data were analysed.OCT4+cells were successfully detected in peripheral blood collected from all four Stage I lung cancer patients.Moreover,the tumour mutational burden(TMB)values observed for OCT4+samples from the same patients were slightly smaller than those of the OCT4−samples;the difference was not statistically significant(P>0.05).Thirteen and six characteristic mutations were found in negative samples and positive samples,respectively.The findings indicate that this methodology provides a potential diagnostic index for the early detection of NSCLC.