Abstract
BackgroundFBXW7, a component of the Skp-Cullin1-F-box, mediates target protein recognition. It is a tumor suppressor gene that plays a role in the regulation of cell cycle exit and reentry via c-Myc, c-Jun and Notch degradation. There are few studies, particularly involving a large patient cohort, that have evaluated FBXW7 during gastric cancer progression.MethodsOur study aimed to evaluate the value of FBXW7 as a clinical marker in gastric adenocarcinoma (GC) patients including a subset treated with postoperative chemotherapy. Quantitative reverse transcription PCR (qRT-PCR) assay was used to measure FBXW7 transcript levels in tumors paired with normal gastric tissue in 24 gastric adenocarcinoma patients. Subsequently, 546 additional GC samples were evaluated from patients that underwent radical gastrectomy, including 118 early stage cases(Stage I) and 428 advanced stage cases (Stages II or III). Amongst the advanced stage patient cases evaluated, 347 received postoperative adjuvant chemotherapy. All 546 gastric adenocarcinoma cases were then evaluated by tissue microarray and immunohistochemistry (IHC) for FBXW7 expression. Clinicopathological features and diagnoses were confirmed by histopathologic evaluation and review of clinical data. Overall survival (OS) was then evaluated in the 546 gastric cancer patients.ResultsBy immunohistologic evaluation, low expression of FBXW7 in primary gastric cancer significantly correlated with poor differentiation of tumor cells. Moreover, low FBXW7 expression was associated with worse survival as well as worse adjuvant chemotherapy response.ConclusionOur findings suggest that FBXW7 may serve as an important predictor in chemotherapeutic responses.
Highlights
F-box and WD repeat domain-containing7 (FBXW7), a component of the Skp-Cullin1-F-box, mediates target protein recognition
FBXW7 can target the degradation of MCL1,cyclin E,Notch,c-Jun and c-Myc, cancer genes related to the proliferation and regulation of gastric cancer cells [10, 11]
FBXW7 mRNA expression in 24 paired gastric adenocarcinomas and noncancerous gastric tissues FBXW7 mRNA expression levels in gastric adenocarcinomas and paired noncancerous gastric tissue in 24 patients were examined by quantitative real time-PCR. 18 s was used as an internal control
Summary
It is a tumor suppressor gene that plays a role in the regulation of cell cycle exit and reentry via c-Myc, c-Jun and Notch degradation. There are few studies, involving a large patient cohort, that have evaluated FBXW7 during gastric cancer progression. FBXW7 can target the degradation of MCL1,cyclin E,Notch,c-Jun and c-Myc, cancer genes related to the proliferation and regulation of gastric cancer cells [10, 11]. FBXW7 down-regulation is found in numerous human malignant tumors, including non-small cell lung cancer, T cells leukemia, bile duct carcinoma, pancreatic carcinoma and endometrial carcinoma [9, 13, 14]. Some studies indicate that low FBXW7 expression is associated with tumor progression and drug resistance in many malignancies [15, 16], there is a paucity of studies examining FBXW7 in gastric cancer. The aim of this study was to explore the relationship between FBXW7 expression and the clinicopathological characteristics as well as chemotherapeutic outcomes in gastric adenocarcinoma patients
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