A Molecular Prognostic Model Predicts Esophageal Squamous Cell Carcinoma Prognosis

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.MethodsWe developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset).ResultsThe expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391–3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256–3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.ConclusionsThis technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

Mithramycin Depletes Specificity Protein 1 and Activates p53 to Mediate Senescence and Apoptosis of Malignant Pleural Mesothelioma Cells

“…Knockdown of SP1 inhibited growth, migration and tumorigenicity of MPM cells, strongly suggesting that SP1 functions as an oncogene in MPM. Whereas SP1 over-expression has been associated with decreased survival of patients with lung and esophageal cancers {Sun, 2014 2914 /id;Cao, 2014 2915 /id}, our micro-array experiments did not reveal an association between SP1 mRNA expression and survival in MPM patients, possibly due to the limited number of samples analyzed, as well as potential discrepancies between mRNA and protein levels detected in MPM specimens using various techniques. Additional experiments demonstrated that MM markedly diminished growth of MPM cells in-vitro and in-vivo via induction of DNA damage, cell cycle arrest and senescence with subsequent apoptosis.…”

Effects of Galectin-1 on Biological Behavior in Cervical Cancer

“…Fascin-1, a member of cytoskeleton proteins, induces the formation of filopodia, lamellipodia, and microspikes of the cell membrane after cross-linking with F-actin, by facilitating the movement, metastasis, and invasion of tumor cells [45]. Multiple investigations have speculated that overexpression of Fascin-1 was associated with a variety of human malignancies, such as pancreatic [46], esophageal [47], breast [48] and colorectal cancers [49]. In line with these notions, our study provided further evidence to satisfy an unmet clinical need.…”

Development of a prognostic model for esophageal cancer based on nine immune related genes

“…The prognostic model for EC has been continuously updated [25][26][27]. In this study, we identi ed 247 up-regulated and 56 down-regulated IRGs in EC and screened out survival-related IRGs.…”