TITLE:
Overexpression of the Six1 Homeobox Gene Is Associated with Diffuse Peritoneal Spread and Larger Residual Disease after Maximal Cytoreductive Effort in Advanced Ovarian Cancer
AUTHORS:
Julia R. Embry-Schubert, Lubna Qamar, Monique Spillman, Michael G. Kelly, Susan A. Davidson, Kian Behbakht
KEYWORDS:
Ovarian Cancer, Homeobox Genes, Six1, Cytoreduction
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.14,
December
3,
2015
ABSTRACT: Study
Design: Between January 2003 and June 2009, we collected fresh tumor and
extracted high-quality RNA from the omental/peritoneal metastases of 47
patients with stage IIB-IV ovarian cancer. Clinical data were abstracted from
the patients’ medical records. Expression of Six1 level by quantitative RT-PCR
was compared with preoperative factors and intraoperative findings using the χ2 test and the Fisher exact test. The effect of Six1 elevation on survival was
assessed with the Kaplan/Meier method. Results: The mean age of patients
enrolled was 60 (range 33 - 84). The histological subtypes were 77% serous
(36/47), 11% endometrioid (5/47), 4% mucinous (2/47), and 4% clear cell (2/47).
Eighty-one percent were optimally cytoreduced. Median Six1 expression for the
samples was 114 fg/ng 18S rRNA and Six1 overexpression, defined as >300
fg/ng 18S rRNA, was observed in 19% of tumors. Six1 expression above sample
median was associated with peritoneal disease (p = 0.049) and inability to
optimally cytoreduce (p = 0.02). Six1 overexpression was associated with
worsened survival in the high grade serous subgroup (43 months versus 71
months, p = 0.039
Log Rank test). Conclusions: Elevated levels of Six1 predict peritoneal disease
and larger residual tumor after maximal cytoreductive effort. Prospective
prediction of surgical cytoreduction using a combination of Six1 expression,
included with other factors, is currently being evaluated.