5.1 DDX3X Expression is Disparate in Human Pan-cancer
Based on the results from TCGA data separate, DDX3X expression was heightened in STAD, and CHOL, since deteriorated in LUAD, LUSC, BRCA, KICH, UCEC, KIRP, BLCA, THCA, THYM tissues distinguished accompanying adjacent rational tissues (Figure 1A). Moreover, we, therefore, examined the expression of DDX3X apathetic malignancy cell lines following the CCLE database (Figure 1B). Because various cancers lack analogous normal tissue controls, we connected the data from the TCGA and GTEx. After combining the data from TCGA and GTEx, the disagreement of DDX3X completed significance in 24 consumed 33 tumor types. DDX3X expression was higher comprehensively in CHOL, ESCA, GBM, GBMLGGT, LGG, PAAD, LAML, and STAD but lower in ACC, BLCA, BRCA, KICH, KIPAN, KIRP, LUAD, LUSC, OV, PRAD, SKCM, TGCT, THCA, UCEC, and UCS (Figure 1C).
5.2 Association of DDX3X Expression With Clinicopathological Features in Different Cancer Types
The connection between DDX3X expression and the clinicopathological characteristics of inmates accompanying various cancers was examined established individual malignancy stages, containing stages 1, 2, 3, and 4. DDX3X expression was universally raised in HNSC, KICH, KIRP, LUSC, and STAD (Figure 2). In contrast, DDX3X expression was severely dropped off in BLCA, BRCA, COAD, THCA, and UCEC. Moreover, DDX3X expression was fixed in a few cancers, containing ESCA, LIHC, KIRC, SKCM, and UVM.
5.3 Prognostic Overall Survival Values of DDX3X in Human Pan-Cancer
Regarding the overall survival (OS) analysis, Cox regression results from 33 types recommended that DDX3X expression was noticeably related to OS in 5 types, containing LAML, LGG, LIHC, KIRC, and SKCM (Figure 3A). The results from the K-M survival curves demonstrated that higher DDX3X expression corresponded with accompanying worse OS in LGG, and LIHC, but with better OS in LAML, KIRC, and SKCM (Figure 3B).
5.4 Prognostic Disease-Specific Survival and Disease-free Interval of DDX3X in Human Pan-Cancer
Moreover, we investigated the DSS and DFI relationship accompanying DDX3X in pan-cancer patients. K-M of DSS analysis indicated that upregulated DDX3X expression harmonized accompanying deficient DSS in victims accompanying KICH, LGG, and PAAD, but accompanying favorable DSS in victims accompanying KIRC, STAD, and OV (Figure 4). K-M of DFI analysis indicated that upregulated DDX3X expression corresponded with accompanying miserable DFI in patients accompanying PCPG, but accompanying favorable DFI in victims accompanying OV and STAD (Figure 4).
5.5 DDX3X is an Independent Prognostic Factor in KIRC and LGG
To further validate whether DDX3X was a liberated prognostic ingredient in cancers, univariate and multivariate Cox regression interpretations were executed to establish miscellaneous clinicopathological characteristics, to a degree age, gender, race, radiation therapy, T stage, N stage, M stage, and TNM stage. Univariate Cox regression evaluation demonstrated that DDX3X expression (p < 0.05), T stage (p < 0.001), N stage (p < 0.001), M stage (p < 0.001), and TNM stage (p < 0.001) were significantly corresponded accompanying OS in KIRC (Figure 5A); DDX3X expression (p < 0.01), age (p < 0.001), grade (p <0.001), and radioactivity-therapy (p < 0.05) were corresponded accompanying OS in LGG (Figure 5D). Multivariate investigation indicated that M stage (p < 0.01) significantly checked to accompany OS in KIRC (Figure 5A); DDX3X expression (p < 0.05), age (p < 0.001), and grade (p <0.01) corresponded accompanying OS in LGG (Figure 5D). In addition, a nomogram was assembled to establish a multivariate study (Figures 5B, E). The C-index and graduated system curve rooted the veracity in envisioning the 1-, 3-, and 5-year continuation rates. The C-index of the prognostic nomogram was 0.848, and 0.821 in KIRC and LGG, separately accompanying moderate veracity (Figures 5C, F).
5.6 DNA Methylation and Genetic Alteration Analysis of DDX3X in Pan-Cancer
A flourishing corpse of deposition advocates that DNA methylation is an epigenetic microscopic mechanism for deoxyribonucleic acid interpretation whatever DNA hypermethylation leads to the inactivation of a comprehensive range of carcinoma suppressor genes. Therefore, we examined the potential link between DNA methylation and DDX3X expression. Concerning the TCGA database, we commemorated that the DNA methylation level of DDX3X was heightened in KIRC, KIRP, LUSC, and PRAD, but deteriorated in TGCT and UCEC based on the UALCAN database (Figure 6A). Additionally, we examined the amendment repetitiveness of DDX3X apathetic tumor types following the cBioPortal database. The top five occurrence rate of hereditary deviations of DDX3X was commemorated in the abdomen, MBN, melanoma, endometrial, and esophageal. Deep erosion existed as the predominant originator of esophageal, yet, mutations were the originator of the surviving four carcinomas (Figure 6B).
5.7 Association of DDX3X Expression and Immune Cell Infiltration in Pan-Cancer
Because immune-infiltrating cells play an outstanding part in tumor initiation and development, we thus estimated the corporation between DDX3X expression and the infiltration levels of six dominant immune cells in 32 types of cancers. Utilizing the data from the TIMER database, the interrelationship between DDX3X expression and the infiltration levels of these immune cells was investigated individually. The outcomes were tacit that DDX3X expression was noticeably tied in accompanying the infiltrating level of B cells in 16 types of tumor, CD4+ T cells in 18 types of tumors, CD8+ T cells in 18 types of tumors, macrophages in 17 types of tumors, neutrophils in 22 types of malignancy, and myeloid decorated with flowers cells in 17 types of malignancy (Figure 7A). In addition, DDX3X interacted accompanying these six types of immune cells in COAD, KIRC, LIHC, PAAD, PRAD, and READ (Figure 7A). To prove the connection between DDX3X expression and infiltration of 38 immune cell subtypes, we resorted to the xCell database. DDX3X expression was negatively related to the infiltration grades of most immune cells in KIRC, SARC, TGCT, THCA, and UCEC (Figure 7B).
5.8 Relationships Between DDX3X Expression and Immune Checkpoint Genes in Pan-Cancer
Because immune checkpoint genes play a substantial function in carcinoma immunotherapy, the interrelationships between DDX3X and immune checkpoint genes, immune inhibitors, and immunostimulators were subsequently investigated. Conspicuously, we commemorated that DDX3X significantly positively corresponded with most immune checkpoint genes like VEGFB but negatively corresponded with most immune checkpoint genes, containing BTN3A1, BTN3A2, CD274, EDNRB, ENTPD1, HMGB1, TLR4, TNFSF4, VEGFA (Figure 8).
5.9 Relationships Between DDX3X Expression and TMB and MSI in Pan-Cancer
TMB and MSI are two emerging biomarkers accompanying the immunotherapy feedback. The relationships between DDX3X expression level and TMB across miscellaneous malignancy types were still investigated. The expression level of DDX3X was strikingly and positively corresponded to accompanying TMB in abundant cancers, containing LUSC, but negatively correlated with accompanying TMB in LIHC, THCA, and UVM. (Figures 9A, C). Additionally, the correlation of DDX3X expression accompanying MSI was further investigated in pan-tumor, among which DLBC, LIHC, THCA, and UVM exhibited an unfavorable equivalence while CHOL, LUSC, READ, and UCEC exhibited a positive interrelationship accompanying DDX3X expression (Figures 9B, C).
5.10 Correlation Between DDX3X Expression Level and Tumor Microenvironment
The expression of DDX3X may be approximately related to immune escape and the micro-environment. The immune score anticipates the response to carcinoma immunotherapy. Analysis of the connection between DDX3X expression and immune scores affirmed that higher DDX3X expression levels cooperate with higher immune scores and stromal obligation (Figure 10).