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Table 3 Clinical Significance of FBXW7 Loss-of-function

From: FBXW7: a critical tumor suppressor of human cancers

Cancer Association between FBXW7 loss-of-function and patient clinical outcomes
B-ALL Pediatric B-ALL: FBXW7 is inversely correlated with disease progression.
T-ALL Overall, FBXW7 is important in disease survival and is linked to specific drug/chemotherapy regime in T-ALL.
Mutation(s) in FBXW7 are not associated with treatment outcomes in newly diagnosed adult T-ALL (UKALLXII/ECOG E2993 regime) or pediatric T-ALL. However, mutation(s) in FBXW7 are linked to better overall survival and event-free survival in LALA-94 and GRAALL-2003 treatment groups.
Activating mutations in Notch (Notch or FBXW7) in pediatric T-ALL lead to better overall response to chemotherapy, but overall patient outcomes differ.
Colorectal Cancer (CRC) FBXW7 mutation(s) do not correlate with 5 year overall survival or disease-free survival in CRC; however, distinct mutations had better overall survival than others.
In metastatic CRC patients (mCRC) missense mutation(s) or loss of FBXW7, demonstrate shorter overall survival and drug resistance to Oxaliplatin, respectively.
FBXW7 mutation(s) show resistance to anti-epidermal growth factor receptor (EGFR) immunotherapy treatment (ie. Cetuximab or Panitumumab).
Esophageal and Gastric Cancers
FBXW7 is associated with muscle-invasive tumor cases (T2–4), lymphatic-invasive tumor cases, and stage II-IV cases.
Copy number loss of FBXW7 is associated with poorer clinical outcome; while Loss of FBXW7 protein expression is correlated with poor prognosis and adjuvant chemotherapy response.
Aberrant FBXW7 mRNA expression is correlated with lymph node metastasis and tumor stage III-IV.
Reduced FBXW7 expression is correlated with lymph node metastasis, tumor size, and poor prognosis in primary gastric cancer.
Lower FBXW7 in ESCC tissue show poorer overall survival and lower 5-year survival.
Targeting of FBXW7 can lead to Cisplatin resistance in human gastric cancer cells.
Hepatocellular Carcinoma
(HCC) and intrahepatic cholangiocarcinoma
Lower FBXW7 expression correlates in HCC patients with higher histological grade and advanced tumor-node-metastasis.
In HCC patients, FBXW7 correlates with tumor differentiation, the incidence of portal or hepatic venous invasion, metastasis, and poorer clinical pathologic features (including large tumor size, high pathological grading, and advanced TNM stage).
Low expression of FBXW7 in both tumor and non-tumor tissue is an independent risk factor for HCC recurrence in patients after hepatectomy.
Reduced FBXW7 expression correlates with tumor progression and poor prognosis in IHCC.
Non-small cell lung cancer (NSCLC) Lower FBXW7 expression is associated with more aggressive cancer and shorter survival time in NSCLC.
FBXW7 down-regulation is associated with EGFR inhibitor-resistance in NSCLC.
Ovarian Carcinoma Lower FBXW7 expression in ovarian carcinomas, compared to borderline or benign tumors.
FBXW7 expression levels were lowest in serious carcinomas, followed by endometrioid carcinomas, clear cell carcinomas, and mucinous carcinomas.
Glioblastoma Lower FBXW7 expression in patients with grade IV glioma.
FBXW7 serves as a prognostic marker in glioblastoma; with levels of FBXW7 correlating with survival.
FBXW7 expression is inversely correlated with glioma histology and positively correlated with patient survival time.
Breast Cancer Higher FBXW7 gene expression correlates with increased disease-free survival in breast cancer patients, especially ER negative and basal subtypes.
Higher FBXW7 expression was associated with increased overall survival in patients with ER negative, ERBB2, and basal subtype tumors.
Higher FBXW7 expression was associated with decreased overall survival in patients with normal-like subtype.
Overall, FBXW7β methylation is associated with favorable prognosis and poorly differentiated tumors in breast cancer.
Pancreatic Cancer Low expression of FBXW7 is an independent poor prognostic factor for pancreatic cancer; low FBXW7 correlated with overall, cancer-specific, and relapse-free survival rates.
Levels of FBXW7 expression are associated with sensitivity to gemcitabine treatment.