Abstract
Data mining of a public transcriptomic rectal cancer dataset (GSE35452) from the Gene Expression Omnibus, National Center for Biotechnology Information identified the melanophilin (MLPH) gene as the most significant intracellular protein transport-related gene (GO:0006886) associated with a poor response to preoperative chemoradiation. An MLPH immunostain was performed on biopsy specimens from 172 rectal cancer patients receiving preoperative chemoradiation; samples were divided into high- and low-expression groups by H-scores. Subsequently, the correlations between MLPH expression and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) were analyzed. MLPH expression was significantly associated with CEA level (p = 0.001), pre-treatment tumor status (p = 0.022), post-treatment tumor status (p < 0.001), post-treatment nodal status (p < 0.001), vascular invasion (p = 0.028), and tumor regression grade (p < 0.001). After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178–46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762–17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.
Highlights
IntroductionOn the basis of current evidence, the standard treatment for patients with advanced rectal cancer involves surgery with preoperative radiation with or without chemotherapy [2]
This finding prompted an investigation of the relationship between MLPH expression and clinicopathologic behavior in rectal cancers after chemoradiation
In multivariate analyses (Table 4), MLPH expression was still associated with lower disease-specific survival (DSS) (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178–46.920; p = 0.003) and metastasis-free survival (MeFS) (HR, 5.621; 95% CI, 1.762–17.931; p = 0.004)
Summary
On the basis of current evidence, the standard treatment for patients with advanced rectal cancer involves surgery with preoperative radiation with or without chemotherapy [2]. These advanced therapeutic options have improved patient survival. 10–20% of patients still experience recurrence or metastasis after initial treatment [3]. These rectal cancer patients with tumor failure may be eligible for salvage treatment, they still face a dismal outcome. It is important to find reliable genetic biomarkers as predictors of the response to preoperative therapy and prognosis, and to aid in personal therapeutic modification
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