A Prognostic Model Based on mRNA Expression Analysis of Esophageal Squamous Cell Carcinoma

Abstract

Background: The aim of this study was to identify prognostic markers for esophageal squamous cell carcinoma (ESCC) and build an effective prognostic nomogram for ESCC.Methods: A total of 365 patients with ESCC from three medical centers were divided into four cohorts. In the discovery phase of the study, we analyzed transcriptional data from 179 cancer tissue samples and identified nine marker genes using edgeR and rbsurv packages. In the training phase, penalized Cox regression was used to select the best marker genes and clinical characteristics in the 179 samples. In the verification phase, these marker genes and clinical characteristics were verified by internal validation cohort (n = 58) and two external cohorts (n = 81, n = 105).Results: We constructed and verified a nomogram model based on multiple clinicopathologic characteristics and gene expression of a patient cohort undergoing esophagectomy and adjuvant radiochemotherapy. The predictive accuracy for 4-year overall survival (OS) indicated by the C-index was 0.75 (95% CI, 0.72–0.78), which was statistically significantly higher than that of the American Joint Committee on Cancer (AJCC) seventh edition (0.65). Furthermore, we found two marker genes (TM9SF1, PDZK1IP) directly related to the OS of esophageal cancer.Conclusion: The nomogram presented in this study can accurately and impersonally predict the prognosis of ESCC patients after partial resection of the esophagus. More research is required to determine whether it can be applied to other patient populations. Moreover, we found two marker genes directly related to the prognosis of ESCC, which will provide a basis for future research.

The Molecular Characterization of Genetic Abnormalities in Esophageal Squamous Cell Carcinoma May Foster the Development of Targeted Therapies

“…Nine of these genes (HSPA6, SP100A12, CACYBP, NOS2, DKK1, DSM, STC2, NGPTL3 and NRF2) defined two ESCC subgroups: a high-risk subgroup with the enrichment of M0 and M2 macrophages and activated mast cells and a low-risk subgroup rich in CD8 T cells and regulatory T cells [51]. A recent study showed that the expression level of two genes may help define the prognosis of ESCC patients: ESCC patients with high PDZK1P1 expression had worse prognoses than those with low expression; in contrast, TM9SF1 expression levels were correlated with better prognoses [52]. The incorporation of the mRNA expression levels of these two genes with TMN staging and age allowed for the development of a prognostic model with good predictive accuracy for ESCC patients [52].…”

“…A recent study showed that the expression level of two genes may help define the prognosis of ESCC patients: ESCC patients with high PDZK1P1 expression had worse prognoses than those with low expression; in contrast, TM9SF1 expression levels were correlated with better prognoses [52]. The incorporation of the mRNA expression levels of these two genes with TMN staging and age allowed for the development of a prognostic model with good predictive accuracy for ESCC patients [52].…”

“…Other studies have evaluated the potential capacity of gene expression analysis to predict responses to neoadjuvant chemotherapy. Thus, Wen at al., through gene expression analysis, identified some genes whose expressions predict responses to neoadjuvant treatments with chemoradiotherapy (CCRT) in ESCC patients; six genes (LIMCH1, SDPR, C1orf226, SLC9A9, GSMM3 and IGSFIo) were downregulated and four genes (MMP1, MMP9, MMP12 and OASL) were upregulated in patients exhibiting a complete response compared with those achieving only a suboptimal response [52]. A simplified three-gene signature (MMP1, LIMCH1 and C1orf226) was able to appropriately predict responses in 81% of tumor cases; particularly, all cases with suboptimal responses were identified, while only 54% of cases with complete responses were predicted [53].…”

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

“…In addition to BC, TM9SF1 has been found to be overexpressed in esophageal and cervical cancer with a speculated link to poorer survival and recurrence rates in some preclinical studies[ 14 , 15 ]. Its role as an oncogene might be due to its effects on the G1 phase.…”

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

“…By establishing an effective prognostic nomogram model for esophageal squamous cell carcinoma, two marker genes were identified that are directly associated with 4-year overall survival of cancer patients, one of which is TM9SF1. The expression value of TM9SF1 gene in cancer patients was found to be significantly higher than that of healthy individuals[ 11 ]. ApostolosZaravinos’ study employed enome-wide microarray analysis, classifying samples based on histology and discovering 17 differentially expressed genes, one of which was TM9SF1.…”