Abstract
TP53 mutation (TP53MUT) is one of the most common gene mutations and frequently occurs in many cancers, especially esophageal carcinoma (ESCA), and it correlates with clinical prognostic outcomes. Nevertheless, the mechanisms by which TP53MUT regulates the correlation between ESCA and prognosis have not been sufficiently studied. Here, in the current research, we constructed a TP53MUT-related signature to predict the prognosis of patients with esophageal cancer and successfully verified this model in patients in the TP53 mutant group, esophageal squamous cell carcinoma group, and adenocarcinoma group. The risk scores proved to be better independent prognostic factors than clinical features, and prognostic features were combined with other clinical features to establish a convincing nomogram to predict overall survival from 1 to 3 years. In addition, we further predicted the tumor immune cell infiltration, chemical drugs, and immunotherapy responses between the high-risk group and low risk group. Finally, the gene expression of the seven-gene signature (AP002478.1, BHLHA15, FFAR2, IGFBP1, KCTD8, PHYHD1, and SLC26A9) can provide personalized prognosis prediction and insights into new treatments.
Highlights
Esophageal carcinoma (ESCA) is the seventh most common malignant tumor globally (Bray et al, 2020), with a 5-year survival rate ranging from 10 to 25% (Stein et al, 2005)
The results illustrated that samples with and without TP53 mutations were obviously clustered in KEGG_DNA_REPLICATION, KEGG_MISSMATCH_REPAIR; KEGG_CELL_CYCLE, KEGG_SMALL_CELL_LUNG_CANCER, GO_ADAPTIVE_IMMUNE _RESPONSE, GO_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE _RESPONSE (Wu et al, 2020), GO_REGULATION _OF_HUMORAL_IMMUNE_RESPONSE, GO_T_HELPER_1_ TYPE_IMMUNE_RESPONSE, and GO_REGULATION_OF_IMMUNE_EFFECTOR_PROCESS, suggesting that the gene associated with TP53MUT can have an immunomodulatory effect on esophageal carcinoma (ESCA) (Figure 1D)
Results illustrated that mutated TP53 was obviously enriched in immune biological functions, suggesting that TP53MUT can have an immunomodulatory effect on ESCA
Summary
Esophageal carcinoma (ESCA) is the seventh most common malignant tumor globally (Bray et al, 2020), with a 5-year survival rate ranging from 10 to 25% (Stein et al, 2005). This type of carcinoma consists of two main subtypes: esophageal adenocarcinoma (ESAD) and esophageal squamous cell carcinoma (ESCC). The incidence of both types of cancer is increasing year on year, so this study investigated the two together (Wei et al, 2015; Deng et al, 2018). We need to further reveal the possible function and mechanism by which this TP53-related signature is mediated in ESCA
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