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. 2022 Jul 7:12:931445.
doi: 10.3389/fonc.2022.931445. eCollection 2022.

High Expression of PARP1 in Tumor and Stroma Cells Predicts Different Prognosis and Platinum Resistance in Patients With Advanced Epithelial Ovarian Cancer

Wei-Wei Zuo  1   2 , Chun-Fang Zhao  3 , Yan Li  4 , Hai-Yan Sun  1 , Guo-Ming Ma  5 , Yue-Ping Liu  6 , Shan Kang  1
Affiliations

High Expression of PARP1 in Tumor and Stroma Cells Predicts Different Prognosis and Platinum Resistance in Patients With Advanced Epithelial Ovarian Cancer

Wei-Wei Zuo et al. Front Oncol. .

Erratum in

Abstract

Objective: This study aimed to explore the roles of PARP1 mRNA and protein expression in platinum resistance and prognosis of EOC patients, and reveal the different roles of PARP1 protein in epithelial tumor and stroma cells.

Methods: The PARP1 mRNA expression of the EOC tissues was examined by RT-qPCR. The impacts of PARP1 expression on prognosis were measured by Kaplan-Meier and Cox regression. Receiver operating characteristic (ROC) curve analysis was employed for calculating the diagnostic value of PARP1 on platinum resistance. The microarray of formalin-fixed, paraffin-embedded (FFPE) tissues was processed for multiplex immunofluorescence to detect the protein levels of PARP1 and cytokeratin (CK).

Results: The PARP1mRNA expression of EOC patients was higher in the platinum-resistant group compared with the sensitive group (P<0.01). Kaplan-Meier analysis demonstrated that high PARP1 mRNA expression was associated with poor survival of EOC patients. In Cox regression analyses, high PARP1 mRNA expression independently predicted poor prognosis (P=0.001, HR=2.076, 95%CI=1.373-3.140). The area under the ROC curve of PARP1 mRNA for predicting the platinum resistance in EOC patients was 0.649, with a sensitivity of 0.607 and specificity of 0.668. Furthermore, the protein expression of PARP1 was higher in the platinum-resistant group than in the sensitive group (P<0.01) and associated with a worse prognosis. Additionally, according to CK labeling, we observed that enhanced expression of PARP1 in the CK+ region was associated with platinum resistance and lower survival, but in CK- region, it predicted a good prognosis and platinum sensitivity.

Conclusion: PARP1 may be a potential biomarker to predict platinum resistance and prognosis for EOC patients, exerting different roles on epithelial tumor and stromal cells.

Keywords: PARP1; advanced epithelial ovarian cancer; cytokeratin; platinum resistance; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PARP1 expression in ovarian tumor and normal tissue and in specimens from sensitive and resistant patients. (A)The differential expression of PARP1 in ovarian tumor and normal ovarian tissues was analyzed by GEPIA. Red colour means ovarian cancer tissues and grey colour means normal tissues; (B) The mRNA expression of PARP1 in EOC samples (Tumor) and normal ovarian tissues (Normal) was tested by qRT-PCR; (C) qRT-PCR was utilized to examine the mRNA expression of PARP1 between Resistant and Sensitive groups; (D) The protein level of PARP1 was detected by immunofluorescence assay of microarray in paraffin-embedded tissue; (E) ROC analysis was used to investigate diagnostic value of PARP1 on platinum resistance of EOC. *P < 0.05, **P < 0.01; EOC, Epithelial ovarian cancer.
Figure 2
Figure 2
The mRNA expression of PARP1 was up-regulated in EOC patients and associated with poor prognosis. (A, B) The PFS and OS in resistant group and sensitive group were compared using Kaplan-Meier analysis; (C, D) The mRNA expression of PARP1 influencing the PFS and OS. PFS, Progression-free survival; OS, Overall survival; EOC, Epithelial ovarian cancer.
Figure 3
Figure 3
The protein level of PARP1 was up-regulated in microarray of formalin-fixed, paraffin-embedded tissues from tumor samples and correlated to poor prognosis. (A) Representive images of PARP1 with high expression (brown and red; Scar bar=100 and 50μm); (B) The protein level of PARP1 influencing the PFS and OS was measured by Kaplan-Meier method. PFS, Progression-free survival; OS, Overall survival; EOC, Epithelial ovarian cancer.
Figure 4
Figure 4
PARP1 predicted prognosis and platinum resistance in epithelial tumor cells and stromal cells. (A) High protein level of PARP1 (red) in CK+ region (white) indicated EOC patients with poor prognosis and platinum resistance (Scar bar=50μm); (B) High protein level of PARP1 in CK- region indicated EOC patients with good prognosis and platinum sensitivity (Scar bar=50μm). CK, Cytokeratins; PFS, Progression-free survival; OS, Overall survival; EOC, Epithelial ovarian cancer. **P < 0.01
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