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310 Chemotherapy reduces PAR glycohydrolase (PARG) expression in high-grade serous ovarian cancer patients
  1. V Lopez Ozuna1,
  2. IY Hachim2,
  3. L Kogan1,
  4. W Gotlieb1 and
  5. A Yasmeen1
  1. 1Segal Cancer Center- Lady Davis Institute of Medical Research- McGill University, Division of Gynecologic Oncology- Jewish General Hospital, Montreal, Canada
  2. 2Research Institute McGill University Health Center- Cancer research program, Department of Medicine, Montreal, Canada


Objectives Evaluate the effect of chemotherapy treatment on PAR glycohydrolase (PARG), other member of poly(ADP-ribose) metabolism, in high-grade serous ovarian cancer patients (HGSOC).

Methods Two HGSOC cohorts were evaluated by immunohistochemistry: 54 chemo-naïve HGSOC patients (45 HGSOC, 9 borderline, 4 normal tissue) and 53 HGSOC chemo-treated patients (44 HGSOC, 9 borderline, 7 normal tissue). In addition, we used in silico analysis to evaluate the effect of PARG mRNA expression in ovarian cancer and its relation with patient outcome.

Results Our results showed that chemo-naïve patients have significant higher levels of PARG expression compared to borderline and normal (62.2%, 44.4% and 0% respectively). Interestingly, these levels were reduced in HGSOC patient samples that have received chemotherapy (45.44%, 44%, 0%, respectively, p<0.03). Indeed, this demonstrated that chemotherapy induces a reduction in PARG expression to levels equal to the borderline tumors. Furthermore, we found a dramatic re-localization of PARG protein to the cytoplasm in chemo-treated patients (100%) compared with chemo-naïve HGSOC samples that were localized in the nucleus (80%,P<0.05).In silico analysis of 1500 ovarian cancer patients revealed that PARG is up-regulated in ovarian cancer in comparison with normal tissue and highly express in advance-metastatic HGSOC. Moreover, its expression in advance disease was associated with shorter overall survival.

Conclusions Our results showed that chemotherapy decreased PARG expression and re-localized it into the cytoplasm. Moreover, our findings highlights the possible use of PARG inhibitors as an adjuvant therapy to treat recurrent ovarian cancer together with chemotherapy and other new-targeted drugs such as PARP inhibitors.

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