Abstract
Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC.
Highlights
Gastric cancer is a common worldwide cancer which is diagnosed in excess of 1 million people every year according to the International Agency for Research on Cancer (IARC)GLOBOCAN project [1]
Epithelial protein lost in neoplasm (EPLIN) expression appeared to have a negative correlation with the depth of tumour infiltration into the stomach wall and it was noted that the combined T1 + T2 group, combined to give a broader overview and to combat low sample numbers in individual groups, had significantly higher levels of EPLIN transcript compared to the more invasive combined T3+T4 group (p = 0.0421) (Figure 1B), though no-significant differences were observed between the individual groups (Table 1)
Our present study explores the significance of EPLIN expression in clinical cohorts of gastric cancer, its usefulness as a prognostic factor and its potential relationship with responsiveness to neoadjuvant chemotherapy (NAC)
Summary
Gastric cancer is a common worldwide cancer which is diagnosed in excess of 1 million people every year according to the International Agency for Research on Cancer (IARC)GLOBOCAN project [1]. Gastric cancer is a common worldwide cancer which is diagnosed in excess of 1 million people every year according to the International Agency for Research on Cancer (IARC). Despite its incidence and mortality decreasing over the past five years, it remains the third most common cause of cancer death [1]. The main failures of cancer treatment are local recurrence and metastasis. The acquisition of chemotherapy resistance is a common reason contributing to treatment failure [2]. Recent systematic review and meta-analysis of the safety and efficacy of third and later line therapy, following failure of initial therapy, in patients with advanced or metastatic gastric or gastroesophageal cancer demonstrated their potential benefit and highlighted the need for focused research on improving patient selection in order to identify those who could benefit from such therapies [3].
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