RESUMEN
Pancreatic adenocarcinoma (PAAD) is a notably aggressive malignancy with limited treatment options and an unfavorable prognosis for patients. We aimed to investigate molecular mechanisms by which Sam's pointed domain-containing ETS transcription factor (SPDEF) exerts effects on PAAD progression. We analyzed differentially expressed genes (DEGs) and their integration with ETS family members using the The Cancer Genome Atlas (TCGA) database, hence identifying SPDEF as a core gene in PAAD. Kaplan-Meier survival analysis confirmed SPDEF's prognostic potential. In vitro experiments validated the association with cell proliferation and apoptosis, affecting pancreatic cancer cell dynamics. We detected increased SPDEF expression in PAAD tumor samples. Our in vitro studies revealed that SPDEF regulates mRNA and protein expression levels, and significantly affects cell proliferation. Moreover, SPDEF was associated with reduced apoptosis and enhanced cell migration and invasion. In-depth analysis of SPDEF-targeted genes revealed four crucial genes for advanced prognostic model, among which S100A16 was significantly correlated with SPDEF. Mechanistic analysis showed that SPDEF enhances the transcription of S100A16, which in turn enhances PAAD cell migration, proliferation, and invasion by activating the PI3K/AKT signaling pathway. Our study revealed the critical role of SPDEF in promoting PAAD by upregulating S100A16 transcription and stimulating the PI3K/AKT signaling pathway. This knowledge deepened our understanding of pancreatic cancer's molecular progression and unveiled potential therapeutic strategies targeting SPDEF-driven pathways.
RESUMEN
Background: The relationship between endocervical and ectocervical margin status and residual or recurrence after cervical intraepithelial neoplasia (CIN) resection has been controversial. We investigated the relationship between the excision margins and residual/recurrence to assess indicators for the scope of resection and the risk of treatment failure by using meta-analysis. Methods: Literature searches were performed in PubMed, Medline, Embase, Central, Wangfang and CNKI databases. Patients after CIN resection were grouped according to whether there was residual or recurrence, and the differences in exposure factors between the two groups were compared. Or they were grouped by exposure factor, and compare the differences in residual and recurrence rates under different grouping conditions. The observed outcome was postoperative residual or recurrence. The risk of bias in the literature was assessed using the Newcastle-Ottawa Scale (NOS). The chi-square test were used for heterogeneity. Subgroup explored the sources of heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Results: A total of 11 studies were included in this study, 8 studies were at low risk of bias and 3 studies were at high risk of bias. The 11 studies included 3065 patients, 774 patients with positive margins and 2,291 patients with negative margins. The rate of residual/recurrence after excision of CIN in patients with positive margins was significantly higher than in patients with negative margins [odds ratio (OR) =3.99, P<0.00001]. There was no heterogeneity among the studies (P=0.16), with publication bias (P<0.05). The residual/recurrence rate was significantly higher in patients with positive endocervical margins than in patients with negative endocervical margins (OR =2.59, P<0.00001). There was no heterogeneity among studies (P=0.78) and no publication bias (P<0.05). There was no significant difference in residual/recurrence rate between positive and negative ectocervical margins (OR =1.14, P=0.36). There was no heterogeneity among studies (P=0.32) and no publication bias (P<0.05). Conclusions: Positive endocervical margins, but not external cervical margins, are risk factors for residual/recurrence of CIN after resection. Close attention to the status of the endocervical margins is recommended. More aggressive treatment and frequent follow-up are needed for patients with positive endocervical margins.
RESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is of great malignancy and high mortality. Identification of effective biomarkers could improve the monitoring of CCA development and attenuate patients' outcomes. OBJECTIVE: The potential of lncRNA TM4SF1-AS1 (TM4SF1-AS1) serving biomarker of CCA was estimated and the underlying mechanism was also investigated. METHODS: A total of 107 pairs of tumor and paracancer tissues were collected from CCA patients. The expression levels of TM4SF1-AS1 and miR-744-3p were analyzed in CCA by PCR, and their clinical significance was estimated by a series of statistical analyses. CCK8 and Transwell assays were used to assess the development-related cellular processes of CCA. The interaction between TM4SF1-AS1 and miR-774-3p was evaluated by cell transfection and dual-luciferase reporter assay. RESULTS: The elevated expression of TM4SF1-AS1 and the declined expression of miR-744-3p were observed in CCA. Both TM4SF1-AS1 and miR-744-3p were found to possess a close association with the malignant progression and poor prognosis of CCA patients. TM4SF1-AS1 was suggested to act as a tumor promoter of CCA, where miR-744-3p was found to mediate the function of TM4SF1-AS1. CONCLUSION: Both TM4SF1-AS1 and miR-744-3p were identified as prognostic biomarkers of CCA. TM4SF1-AS1 served as tumor promoter of CCA via modulating miR-744-3p.
