GALNT14 genotype, α-fetoprotein and therapeutic side effects predict post-chemotherapy survival in patients with advanced hepatocellular carcinoma

Abstract

Abstract. In addition to targeted agents, chemotherapy is currently considered to be a treatment option for patients with advanced hepatocellular carcinoma (HCC); however, it is associated with severe side effects that may limit its clinical use. UDP-N-acetyl-α-D-galactosamine:polypep tide N-acetyl-galactosaminyltransferase 14 (GALNT14) genotype was previously identified as a prognostic marker for HCC patients receiving 5-fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy. The present study aimed to assess clinical parameters and on-treatment side effects as effective predictors for favorable prognosis. A total of 118 patients with HCC receiving split-dose FMP were retrospectively enrolled. The clinical parameters, side effects and GALNT14 genotype were analyzed. The independent predictors for time-to-progression (TTP) and overall survival (OS) were assessed using Cox proportional hazards models. Following categorization, the Kaplan-Meier method was used to compare survival outcomes. Pretreatment α-fetoprotein (AFP) ≤2,800 ng/ml (median level), GALNT14 'TT' genotype, on-treatment leukopenia and absence of vomiting were identified as independent predictors of a favorable TTP (P= 0.001, 0.035, 0.008 and 0.009, respectively) and OS (P= 0.028, 0.006, 0.027 and 0.013, respectively). A total of 59 patients with AFP ≤2,800 ng̸ml exhibited longer median TTP and OS (3.11 vs. 1.75 months, P<0.001; and 8.14 vs. 3.79 months, P<0.001, respectively). A total of 30 patients with the GALNT14 'TT' genotype exhibited longer median TTP and OS (3.11 vs. 2.11 months, P= 0.014; and 5.75 vs. 3.93 months, P=0.001, respectively). Finally, 9 patients (9/118; 7.6%) with all four favorable factors exhibited the longest median TTP and OS (10.64 vs. 2.07 months, P= 0.002; and 25.50 vs. 4.50 months, P<0.001, respectively). In conclusion, the AFP level and the GALNT genotype may be considered as pre-therapeutic predictors of a favorable response. When combined with on-treatment leukopenia and absence of vomiting, a subgroup of patients with excellent outcome may be identified.

GALNT14 genotype is associated with perineural invasion, lymph node metastasis and overall survival in resected cholangiocarcinoma

“…A leading single nucleotide polymorphism, rs9679162, was identified to be associated with chemotherapy response, time-to-tumor progression and overall survival in a previous study of patients with HCC at Barcelona Clinic Liver Cancer (BCLC) Stage C (16,17). The genotypes were also identified to correlate with the therapeutic response in TACE-treated patients with HCC at BCLC Stage B (18).…”

GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

“…In patients with advanced hepatocellular carcinoma receiving palliative chemotherapy, the “TT” genotype predicted a favorable treatment outcome. 12 , 13 The product of GALNT14 gene was a catalytic enzyme that catalyzed O -glycosylation of many proteins including the death receptor (DR)-4 and -5. Because the O -glycosylation of DR 4 of 5 increased their sensitivity to apoptotic signals, this genotype association of chemotherapy sensitivities might not be restricted to hepatocellular carcinoma.…”

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

“…Cancer cells possess the ability to evade apoptosis, rendering cytotoxic drugs ineffective, an activity that is considered one of the challenges in cancer treatment. Chemotherapeutics induce cancer cells to undergo apoptosis through different pathways [38]. GALNT14 shows a strong restraint to the sensitivity of the proapoptotic ligand Apo2L/TRAIL in pancreatic carcinoma, non-small cell lung cancer and melanoma [39].…”