PLoS ONE: Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression (clear cell ovarian/high grade)

PLoS ONE: Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression

"....According to FIGO grading classification, high-grade ovarian tumor cells are usually poorly histological differentiated [20], grow faster and highly metastatic [7]. In addition, prognosis of high-grade ovarian tumor is poor thereafter it often associates with poor survival rate [21], [22].The clear cell subtype ovarian cancer accounts for approximately 6% of all epithelial ovarian tumors and most cases of this subtype are high-grade tumor exhibiting an aggressive phenotype [3], [22], [23]. Our study showed that both mRNA and protein levels of PITX2 was frequently upregulated in ovarian cancer particularly in the high-grade and clear cell subtypes, indicating that PITX2may play an important role in driving aggressive phenotypes in ovarian cancer.....

paywalled - Gynecologic Oncology - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum

ScienceDirect.com - Gynecologic Oncology - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum

Abstract

Objective

Approximately 20% of patients receiving platinum-based chemotherapy for epithelial ovarian cancer (EOC) are refractory or develop early recurrence. Identifying these patients early could reduce treatment-associated morbidity and allow quicker transfer to more effective therapies. Much attention has focused on ERCC1 as a potential predictor of response to therapy because of its essential role in the repair of platinum-induced DNA damage. The purpose of this study was to accurately measure protein levels of ERCC1 and its essential binding partner XPF from patients with EOC treated with platinum-based therapy and determine if protein levels correlate with mRNA levels, patient genotypes or clinical outcomes.

Methods

ERCC1 and XPF mRNA and protein levels were measured in frozen EOC specimens from 41 patients receiving intraperitoneal platinum-based chemotherapy using reverse transcription polymerase chain reaction and western blots. Genotypes of common nucleotide polymorphisms were also analyzed. Patient outcomes included progression free (PFS) and overall survival (OS).

Results

Expression of ERCC1 and XPF were tightly correlated with one another at both the mRNA and protein level. However, the mRNA and protein levels of ERCC1 were not positively correlated. Likewise, none of the SNPs analyzed correlated with ERCC1 or XPF protein levels. There was an inverse correlation between mRNA levels and patient outcomes.

Conclusion

Neither genotype nor mRNA levels are predictive of protein expression. Despite this, low ERCC1 mRNA significantly correlated with improved PFS and OS.

BRCA1 mRNA expression and outcome to neoadjuvant cisplatin-based chemotherapy in bladder cancer

Abstract

Background: Neoadjuvant chemotherapy has shown a modest benefit in muscle-invasive bladder cancer patients; however, the subset of patients most likely to benefit has not been identified. BRCA1 plays a central role in DNA repair pathways and low BRCA1 expression has been associated with sensitivity to cisplatin and longer survival in lung and ovarian cancer patients.

Patients and methods: We assessed BRCA1 messenger RNA expression levels in paraffin-embedded pre-treatment tumor samples obtained by transurethral resection from 57 patients with locally advanced bladder cancer subsequently treated with neoadjuvant cisplatin-based chemotherapy. BRCA1 levels were divided into terciles and correlated with pathological response and survival....