FBXL7 Upregulation Predicts a Poor Prognosis and Associates with a Possible Mechanism for Paclitaxel Resistance in Ovarian Cancer

Hui-Wen Chiu, Jeng-Shou Chang, Hui-Yu Lin, Hsun-Hua Lee, Chia-Hao Kuei, Che-Hsuan Lin, Huei-Mei Huang, Yuan-Feng Lin

Research output: Contribution to journalArticle

Abstract

Paclitaxel (PTX) is a common regimen used to treat patients with ovarian cancer. Although approximately 60% of ovarian cancer patients exhibit a pathologic complete response (pCR), approximately 40% of patients appear to be insensitive to PTX adjuvant therapy. Thus, identifying a useful biomarker to predict pCR would be of great help to ovarian cancer patients who decide to receive PTX treatment. We found that FBXL7 was downregulated in OVSAHO (PTX-sensitive) but upregulated in KURAMOCHI (PTX-resistant) cells after PTX treatment at cytotoxic concentrations. Moreover, our data showed that the fold change of FBXL7 expression post-treatment with PTX was causally correlated with the 50% inhibitory concentrations (IC50) of PTX in a panel of ovarian cancer cell lines. In assessments of progression-free survival probability, high levels of FBXL7 transcript strongly predicted a poor prognosis and unfavorable response to PTX-based chemotherapy in patients with ovarian cancer. The knockdown of FBXL7 predominantly enhanced the cytotoxic effectiveness of PTX on the PTX-resistant KURAMOCHI cells. FBXL7 may be a useful biomarker for predicting complete pathologic response in ovarian cancer patients who decide to receive post-operative PTX therapy.

Original languageEnglish
JournalJournal of Clinical Medicine
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 6 2018

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