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Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in locally advanced gastric cancer patients after surgery with curative intent.

ABSTRACT: Amphiregulin (AREG) and epiregulin (EREG) are important ligands to the epithelial growth factor receptor, which is involved in the regulation of progression and stemness in gastric cancer (GC). This study investigated whether frequent single nucleotide polymorphisms (SNPs) in genes of AREG and EREG are associated with recurrence-free survival and overall survival in patients with locally advanced GC.SNPs with a minor allele frequency of at least 10% were analyzed using direct DNA sequencing in two independent study populations.The minor allele of AREG rs1615111 was associated with a significantly higher 3-year recurrence rate and lower 3-year survival rate [hazard ratio (HR)=2.21 and 2.35, respectively] compared with patients homozygous for the dominant allele G. The value for overall survival could be validated with a HR of 2.54 (P=0.018) in an independent cohort. Patients homozygous for the minor allele A of EREG rs12641042 had a significantly higher 3-year survival rate than patients with allele C (HR 0.48; P=0.034), but significance was lost in multivariable analysis (P=0.066). The value of rs12641042 could not be validated (P=0.98). Exploratory multivariable subgroup analysis showed the strongest prognostic value for rs1615111 in tumors with a diffuse histology (Pfor interaction=0.004).AREG rs1615111, located in the AREG genomic region, can significantly define different prognostic cohorts in locally advanced GC. This value is most evident in GC patients with diffuse histology, which might be relevant as none of the trials testing epithelial growth factor receptor inhibitors has been enriched for diffuse histology or a molecularly defined population.

SUBMITTER: Wakatsuki T

PROVIDER: S-EPMC4190127 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in locally advanced gastric cancer patients after surgery with curative intent.

Wakatsuki Takeru T Stintzing Sebastian S Zhang Wu W Yang Dongyun D Azuma Mizutomo M Ning Yan Y Yamauchi Shinichi S Matsusaka Satoshi S Volz Nico B NB Sunakawa Yu Y Koizumi Wasaburo W Watanabe Masahiko M Barzi Afsaneh A El Khoueiry Anthony B AB Shah Manish A MA Lenz Heinz-Josef HJ

Pharmacogenetics and genomics 20141101 11

<h4>Objective</h4>Amphiregulin (AREG) and epiregulin (EREG) are important ligands to the epithelial growth factor receptor, which is involved in the regulation of progression and stemness in gastric cancer (GC). This study investigated whether frequent single nucleotide polymorphisms (SNPs) in genes of AREG and EREG are associated with recurrence-free survival and overall survival in patients with locally advanced GC.<h4>Methods</h4>SNPs with a minor allele frequency of at least 10% were analyze ...[more]

PMID: 25203737

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Project description:BackgroundAlthough general agreement exists on palliative surgery with intent of symptom palliation in advanced gastric cancer (AGC), the role of non-curative surgery for incurable, asymptomatic AGC is hotly debated. We aim to clarify the role of non-curative surgery in patients with incurable, asymptomatic AGC under the first-line chemotherapy.MethodsA total of 737 patients with incurable, asymptomatic advanced gastric adenocarcinoma between January 2008 and May 2012 at the Sun Yat-sen University Cancer Center were retrospectively analyzed, comprising 414 patients with non-curative surgery plus first-line chemotherapy, and 323 patients with first-line chemotherapy only. The clinicopathologic data, survival, and prognosis were evaluated, with propensity score adjustment for selection bias.ResultsThe median overall survival (OS) outcomes significantly favored non-curative surgery group over first-line chemotherapy only group in entire population (28.00 versus 10.37 months, P = 0.000), stage 4 patients (23.87 versus 10.37 months, P = 0.000), young patients (28.70 versus 10.37 months, P = 0.000) and elderly patients (23.07 versus 10.27 months, P = 0.031). The median OS advantages of non-curative surgery over first-line chemotherapy only were also maintained when the analyses were restricted to single organ metastasis (P = 0.001), distant lymph node metastasis (P = 0.002), peritoneal metastasis (P = 0.000), and multi-organ metastasis (P = 0.010). Significant OS advantages of non-curative surgery over chemotherapy only were confirmed solid by multivariate analyses before and after adjustment on propensity score (P = 0.000). Small subsets of patients with surgery of single metastatic lesion after previous curative gastrectomy, and with surgery of both primary and single metastatic sites showed sound median OS.ConclusionsThere is a role for non-curative surgery plus first-line chemotherapy for incurable, asymptomatic AGC, in terms of survival. Randomized controlled trials are warranted to fill a gap in knowledge about the value of metastectomy and patient selection strategies.

Project description:For locally advanced head and neck squamous cell carcinoma (HNSCC), therapeutic decisions depend on comorbidity or age. We estimated the treatment outcomes of patients with different Charlson comorbidity index (CCI) scores and ages to determine whether aggressive treatment improves survival.Data from the Taiwan National Health Insurance and cancer registry databases were analyzed, and we included >20-year-old patients with American Joint Committee on Cancer (AJCC) stage III or IV HNSCC (International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9) undergoing surgery, chemotherapy (CT), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), sequential CT and RT, or surgery with adjuvant treatment. The exclusion criteria were a past cancer history, distant metastasis, AJCC stage I or II, missing sex data, an age < 20 years, nasopharyngeal cancer, in situ carcinoma, sarcoma, and HNSCC recurrence. The index date was the date of first HNSCC diagnosis, and comorbidities were scored using the CCI. The enrolled patients were categorized into Group 1 (curative-intent aggressive treatments) and Group 2 (best supportive care or palliative treatments).We enrolled 21,174 stage III or IV HNSCC patients without distant metastasis (median follow-up, 3.25 years). Groups 1 and 2 comprised 18,584 and 2232 patients, respectively. After adjustment for age, sex, and clinical stage, adjusted hazard ratios (95% confidence intervals) of overall death in Group 1 were 0.33 (0.31-0.35), 0.34 (0.31-0.36), and 0.37 (0.28-0.49), and those of all-cause death among patients undergoing curative surgical aggressive treatments were 1.13 (0.82-1.55), 0.67 (0.62-0.73), and 0.49 (0.46-0.53) for CCI scores of ?10, 5 to 9, and <5, respectively.Aggressive treatments improve survival in elderly (?65 years) and critically ill HNSCC patients. Curative nonsurgical aggressive treatments including definitive RT or CCRT might be suitable for HNSCC patients with CCI scores ?10.

Dataset Information

Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in locally advanced gastric cancer patients after surgery with curative intent.

Publications

Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in locally advanced gastric cancer patients after surgery with curative intent.

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