A five-gene signature for predicting overall survival of esophagus adenocarcinoma

Abstract

Esophageal adenocarcinoma (EAC) is common and aggressive with increasing trend of incidence. Urgent need for an effective signature to assess EAC prognosis and facilitate tailored treatment is required. Differentially expressed mRNAs (DEMs) were identified by analyzing EAC tissues and adjacent normal samples from The Cancer Genome Atlas (TCGA). Then univariate regression analyses were performed to confirm prognostic DEMs. We used least absolute shrinkage and selection operator (LASSO) to build a prognostic mRNA signature whose performance was assessed by Kaplan–Meier curve, receiver operating characteristic (ROC). GSE72874 were used as an external test set. The performances of the signature were also validated in internal TCGA and external test sets. Gene set enrichment analysis (GSEA) and tumor immunity analysis were performed to decipher the biological mechanisms of the signature. A 5-mRNA signature consisted of SLC26A9, SINHCAF, MICB, KRT19, and MT1X was developed to predict prognosis of EAC. The 5-mRNA signature was promising as a biomarker for predicting 3-year survival rate of EAC in the internal test set, the entire TCGA set, and the external test set with areas under the curve (AUC) = 0.849, 0.924, and 0.747, respectively. Patients were divided into low- and high-risk groups based on risk scores of the signature. The high-risk group was mainly associated with cancer-related pathways and low levels of B cell infiltration. The 5-mRNA prognostic signature we identified can reliably predict prognosis and facilitate individualized treatment decisions for EAC patients.

Development of a prognostic signature of patients with esophagus adenocarcinoma by using immune-related genes

“…Although the previous studies have explored the predictive value of IRGs in the EC or EAC [18][19][20], the predicted signature we constructed (P = 7.26e−07, the AUC of 1-, 3-and 5-year is 0.871, 0.924 and 0.961 respectively) is more reliable than similar studies, and the prognostic ability of this signature is also assessed in the external test set GSE72874 (P = 1.201e−03). Moreover, compared with the study of Lan et al [20], we focus more on which IRGs may participate and promote the occurrence of EAC.…”

“…Recently, prognostic signatures based on IRGs have been constructed in a variety of tumors to develop individualized immune characteristics and improve the prognostic evaluation in immunotherapy, such as non-squamous non-small cell lung cancer [15], glioma [16], and hepatocellular carcinoma [17]. Although the previous studies have explored the predictive value of IRGs in the EC or EAC, the accuracy of each signature is different, and the IRGs included are difference [18][19][20]. Therefore, are there other differentially expressed immune-related genes (DEIRGs) that affect the prognosis of EAC patients?…”

General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers

“…Two genes, SLC26A9 and TMC8, were identified as gene signatures for EBVaCAs because these two genes were upregulated in all EBV-positive cell lines and tumor tissues. Transcriptomics showed that the combination of SLC26A9 and the other four genes, SINHCAF, MICB, KRT19, and MT1X, became a gene signature that predicts the overall survival of esophageal adenocarcinoma [ 40 ]. The combination of SLC26A9 with AP002478.1, BHLHA15, FFAR2, IGFBP1, KCTD8, and PHYHD1 was also identified as a gene signature for personalized prognosis prediction and targeted therapy of esophageal adenocarcinoma [ 41 ].…”

“…SLC26A9 is a member of the solute-linked carrier 26 (SLC26) anion transporter family and is mainly expressed in epithelial cells. SLC26A9 functions uniquely as a chloride channel with minimal conductance to bicarbonate [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. However, the role of SLC26A9 in cancer has not yet been elucidated.…”