Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.

Background Aberrant expression of long noncoding RNA (lncRNA) SLC26A4 antisense RNA 1 (SLC26A4-AS1) plays an important role in some cancer types. However, the clinical significance of SLC26A4-AS1 in patients with breast cancer (BC) and the possible regulatory mechanisms of SLC26A4-AS1 are unclear. Material/Methods Statistical analysis was used to assess the correlation between SLC26A4-AS1 expression and patients’ clinical characteristics. The Kaplan-Meier method and Cox regression analysis were used to assess the correlation between SLC26A4-AS1 expression and prognosis. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were used to investigate the possible regulatory mechanisms of SLC26A4-AS1. Results Low SLC26A4-AS1 expression in BC was associated with age ( P <0.001), estrogen-receptor status ( P <0.001), PAM50 ( P <0.001), and menopause status ( P <0.001). Low SLC26A4-AS1 expression predicted a poorer overall survival (OS) (hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.40–0.78; P =0.001) and disease-specific survival (DSS) (HR: 0.57; 95% CI: 0.37–0.88; P=0.011). Also, SLC26A4-AS1 expression (HR: 0.298; 95% CI: 0.154–0.579; P <0.001) was independently correlated with OS in patients with BC. SLC26A4-AS1 was related to CYP2E1 reactions, protein export, mitochondrial_ciii_assembly, formation of adenosine triphosphate by chemiosmotic coupling, budding and maturation of HIV virion, cristae formation, biocarta proteasome pathway, endosomal sorting complex required for transport, and histone modification. SLC26A4-AS1 expression was associated with some types of immune infiltrating cells. Conclusions SLC26A4-AS1 expression was significantly associated with poor survival and immune infiltration in patients with BC. It may be a promising prognostic biomarker for BC.

Background It is unclear whether the long non-coding RNA (lncRNA) OTX2 antisense RNA 1 (OTX2-AS1) plays a pivotal role in gastric cancer (GC). An analysis of The Cancer Genome Atlas (TCGA) database data and bioinformatics was used to explore the relationship between OTX2-AS1 and GC in the current study. Methods We evaluated the relationship between clinical features and OTX2-AS1 expression, prognostic factors, and the significant involvement of OTX2-AS1 in function using various statistical methods, such as Kaplan–Meier method, Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. GC cell lines were tested for OTX2-AS1 expression using qRT-PCR. Results A high level of OTX2-AS1 expression was significantly and negatively associated with Helicobacter pylori ( H pylori) infection in GC patients ( P = .006) and predicted a poorer overall survival (OS) (HR: 1.54; 95% CI: 1.10-2.14; P = .011), progression-free interval (PFI) (HR: 1.75; 95% CI: 1.22-2.51; P = .002) and disease-specific survival (DSS) (HR: 1.85; 95% CI: 1.21-2.85; P = .005) in GC patients. There was an independent correlation between OTX2-AS1 expression (HR: 1.771; 95% CI: 1.164-2.696; P = .008) and OS in patients with GC. There were differential enrichments for the OTX2-AS1 high expression phenotype in the olfactory transduction, G alpha (s) signaling events, keratinization, olfactory signaling pathway, and preimplantation embryo. OTX2-AS1 expression may be related to certain immune-infiltrating cells. Compared to gastric epithelial cells (GES-1), GC cell lines showed a significant increase in OTX2-AS1 expression. Conclusion There was a significant association between OTX2-AS1 expression in GC patients and poor survival, suggesting that it may be a useful biomarker for prognosis and immunotherapy outcome of stomach adenocarcinoma (STAD) in GC.

Background There is no clear information regarding the role of FAM181A antisense RNA 1 (FAM181A-AS1) in lung adenocarcinoma (LUAD). We explored the relationship between FAM181A-AS1 and LUAD using bioinformatics analysis and experimental validation in this study. Methods Statistics and databases were used to evaluate the relationship between clinical features in LUAD patients and FAM181A-AS1 expression, prognostic factors, regulation network, and immune infiltration of FAM181A-AS1 in function. LUAD cell lines were tested for FAM181A-AS1 expression using qRT-PCR. Results FAM181A-AS1 showed significantly low expression in LUAD patients. Low FAM181A-AS1 expression predicted a poorer overall survival (OS) (HR: 0.66; 95% CI: 0.49–0.88; P=0.005) and disease specific survival (DSS) (HR: 0.64; 95% CI: 0.44–0.92; P=0.017) of LUAD patients. There was also an independent correlation between low FAM181A-AS1 expression (HR: 0.547; 95% CI: 0.350–0.857; P=0.008) and OS in LUAD patients. The FAM181A-AS1 high-expression phenotype was differentially enriched for M phase, cellular senescence, cell cycle checkpoints, chromatin modifying enzymes, ESR-mediated signaling, DNA repair, G2/M checkpoints, HCMV infection, and DNA double-strand break repair. A correlation was found between the expression of FAM181A-AS1 and immune infiltrating cells. A significant decrease in FAM181A-AS1 expression was observed in LUAD cell lines compared to Beas-2B. Conclusion There was a significant association between low FAM181A-AS1 expression in LUAD patients and poor survival and immune infiltration. The FAM181A-AS1 gene may provide a useful biomarker for LUAD prognosis and immunotherapy response.

Background. The Distal-Less homeobox (DLX) gene family plays an important role in several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family and immune in ltration in colon cancer (COAD) have not been systematically reported.Methods. We used Wilcoxon rank sum test and t-test to assess DLX gene family expression between COAD tissues and unpaired normal colon tissues, cBioPortal to analyze DLX gene family variants, R (version 3.6.3) to analyze DLX gene expression in COAD and the relationship between DLX gene family expression and clinical features and correlation heat map, the survival package [version 3.2-10] and the Cox regression module to assess the prognostic value of the DLX gene family, the pROC package [version 1.17.0.1] to analyze the diagnostic value of the DLX gene family, the R ( version 3.6.3) to analyze the possible regulatory mechanisms of DLX gene family members and related genes, the GSVA package [version 1.34.0] to analyze the relationship between the DLX gene family and immune in ltration, and the ggplot2 [version 3.3.3], and survminer package [version 0.4.9] and clusterPro ler package [version 3.14.3] for visualization. Results. DLX 2/3/4/5/6 were signi cantly upregulated in COAD patients. The expression of DLX family was associated with M stage, pathologic stage, primary therapy outcome, residual tumor, lymphatic invasion, T stage, N stage, age, perineural invasion, and history of colon polyps. DLX2/5 were independently correlated with the prognosis of COAD in multivariate analysis. DLX1/2/3/4/5/6 were involved in the development and progression of COAD by participating in immune in ltration and pathways, including breast cancer, gastric cancer, Hippo signaling pathway, Wnt signaling pathway, signaling pathways regulating pluripotency of stem cells, basal cell carcinoma, melanoma, and staphylococcus aureus infection. Conclusion. The DLX gene family can be used as potential diagnostic or prognostic biomarkers and therapeutic targets for COAD.