Abstract
Pancreatic ductal adenocarcinoma (PDA) is notorious for its poor prognosis. The current mainstay of treatment for PDA is surgical resection followed by adjuvant chemotherapy. However, it is difficult to predict the post-operative outcome because of the lack of reliable markers. The single-nucleotide polymorphism (SNP) of N-acetylgalactosaminyltransferase14 (GALNT14) has been proven to predict the progression-free survival (PFS), overall survival (OS) and response to chemotherapy in various types of gastrointestinal (GI) cancers. However, its role in PDA has not been studied. This study aims to investigate whether the GALNT14 SNP genotype can be a prognostic marker for PDA. A cohort of one hundred and three PDA patients having received surgical resection were retrospectively enrolled. GALNT14 genotypes and the clinicopathological parameters were correlated with postoperative prognosis. The genotype analysis revealed that 19.4%, 60.2% and 20.4% of patients had the GALNT14 “TT”, “TG” and “GG” genotypes, respectively. The patients with the “GG” genotype had a mean OS time of 37.1 months (95% confidence interval [CI]: 18.2–56.1) and those with the “non-GG” genotype had a mean OS time of 16.1 months (95% CI: 13.1–19.2). Kaplan–Meier analysis showed that the “GG” genotype had a significantly better OS compared to the “non-GG” genotype (p = 0.005). However, there was no significant difference between the “GG” and “non-GG” genotypes in PFS (p = 0.172). The baseline characteristics between patients with the “GG” and “non-GG” genotypes were compared, and no significant difference was found. Univariate followed by multivariate Cox proportional hazard models demonstrated the GALNT14 “GG” genotype, negative resection margin, and locoregional disease as independent predictors for favorable OS (p = 0.003, p = 0.037, p = 0.021, respectively). Sensitivity analysis was performed in each subgroup to examine the relationship of GALNT14 with different clinicopathological variables and no heterogeneity was found. The GALNT14 “GG” genotype is associated with favorable survival outcome, especially OS, in patients with resected PDA and could serve as a prognostic marker.
Highlights
Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer with poor prognosis, characterized by insidious clinical presentation and limited therapeutic options
This study aims to investigate whether the GALNT14 single-nucleotide polymorphism (SNP) genotype can be a prognostic marker for PDA
The analysis of 103 PDA patients showed that 19.4%, 60.2% and 20.4% had the GALNT14 “TT”, “TG” and “GG” genotypes, respectively
Summary
Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer with poor prognosis, characterized by insidious clinical presentation and limited therapeutic options. Investigations in experimental therapeutics will likely identify better regimens for PDA patients in the future, biomarker discovery is a complementary research strategy that may have a positive impact on personalized therapeutic strategies [2]. Carbohydrate antigen 19-9 (CA19-9) remains the only U.S Food and Drug Administration (FDA)-approved biomarker for PDA though some shortcomings still exist [1,3]. Various biomarkers have been investigated in the fields of diagnosis, prediction, and prognosis for PDA [4,5,6]. Despite tremendous dedication in studies of PDA biomarkers, challenges remain owing to difficult tissue acquisition, inadequate robustness plus standardized procedures, and low sensitivity or specificity of these tools [1]. There is no perfectly reliable indicator to predict the outcome of PDA patients nowadays [1,3,8]
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