Neutrophil extracellular traps enhance platinum resistance in ovarian cancer via SHP-1 activation.

The poor prognosis of ovarian cancer is largely due to platinum resistance. It has been demonstrated that nucleotide excision repair (NER) involving centrin-2(CETN2) is connected to platinum resistance in ovarian cancer. The molecular mechanism of CETN2 in ovarian cancer and the mechanism affecting the outcome of chemotherapy are unknown. The protein-protein interaction (PPI) network was mapped after obtaining the interacting proteins of CETN2, and the interacting genes were subjected to enrichment analysis. To examine the relationship between CETN2 and platinum resistance, gene microarray data and clinical data related to platinum resistance in ovarian cancer were downloaded. The possible signaling pathway of CETN2 was investigated by Gene set enrichment analysis (GSEA). Immune infiltration analysis was performed. Immunohistochemistry (IHC) and quantitative real-time PCR (QRT-PCR) were used to examine the expression of CETN2 in clinical samples in relation to the effectiveness of chemotherapy. The capacity of CETN2 to predict chemotherapy results was proven by receiver operating characteristic (ROC) curves after the construction of two prediction models, the logistic regression model and the decision tree model. The impact of CETN2 on prognosis was examined using the Kaplan-Meier technique. CETN2 was associated with NER, oxidative phosphorylation (OXPHOS) and cell cycle pathways in ovarian cancer drug-resistant samples. In clinical samples, CETN2 showed its possible correlation with immune infiltration. The protein expression level of CETN2 was significantly higher in platinum-resistant patients than that in platinum-sensitive patients, and the expression level had some predictive value for chemotherapy outcome, and high CETN2 protein expression was associated with poorer progression-free survival. CETN2 protein had a significant effect on ovarian cancer platinum sensitivity and prognosis, which may be related to the activation of NER, OXPHOS and cell cycle pathways upon CETN2 upregulation. Further research is necessary to determine the therapeutic application value of CETN2, which may be a new biomarker of chemoresponsiveness.

Ovarian cancer (OC) is the most lethal gynecological cancer in women in the United States. Advances in surgery and chemotherapy have not significantly changed the overall survival rate of OC for the last few decades, which highlights the need for new therapeutic strategies. Platinum drug resistance and refractory disease pose major challenges in treating this disease and are major factors contributing to the poor survival rate of OC patients. Although most patients initially respond to platinum based chemotherapy, about 80% of cases present with recurrent disease, develop platinum resistance, and die with the advanced disease. Considering the heterogeneity, small fractions of the cells could be inherently resistant to chemotherapy and/or dormant and exhibit stem-like cell properties, contributing to the resistant phenotype and disease recurrence. Although the Cancer stem cell (CSC) theory of therapeutic resistance proposes that the proportion of CSCs correlate to enhanced chemoresistance and early disease recurrence, the specific molecular mechanisms that regulate tumor cell behavior (stemness) and integrate signaling networks with aberrant oncogenic signaling in OC cells are not known. Our analysis of clinical samples revealed upregulation of Rad6, an E2 ubiquitin conjugating enzyme, in more than 80% of ovarian tumors compared to normal ovarian tissues. Upregulation of Rad6 also correlated well with tumor progression. Further analysis of molecular pathways in OC cells revealed a strong correlation between Rad6 upregulation and increased β-catenin and hedgehog signaling, stem cell like characteristics and platinum resistance. Downregulation of Rad6 using siRNAs or inhibition of its catalytic activity by a small molecule inhibitor, attenuated carboplatin induced monoubiquitination of its target proteins such as histone 2B, PCNA and proteins of the Fanconi anemia pathway thereby sensitizing OC cells to carboplatin. Interestingly, inhibition of Rad6 alone in OC cells induced replication stress and reduced cell survival and proliferation by arresting cells in the G2/M phase. Moreover, inhibition of Rad6 in various OC cell lines reduced expression of β-catenin, Gli1 and several OC stem cell markers. Moreover, Rad6 plays an important role in the activation of the trans-lesion synthesis (TLS) pathway by monoubiquitinating PCNA and in the activation of the Fanconi Anemia (FA) DNA repair pathway. These are critical mechanisms for cells to repair DNA crosslinks induced by platinum drugs. Together with these observations, our data suggest that inhibition of Rad6 could be a viable therapeutic target for overcoming platinum resistance and disease recurrence in ovarian cancer. Citation Format: Sebastian M. Spencer, Ranganatha R. Somasagara, Kaushlendra Tripathi, David W. Clark, Hend Kothayer, Andrew D. Westwell, Rodney P. Rocconi, Komaraiah Palle. Preclinical evaluation of Rad6 inhibition to overcome platinum resistance in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3734.

Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer

The cytoskeleton plays an important role in platinum resistance in ovarian cancer. Tropomodulin 3 (TMOD3) is critical in the development of many tumors, but its role in the drug resistance of ovarian cancer remains unexplored. By analyzing data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, this study compared TMOD3 expression in ovarian cancer and normal tissues, and examined the expression of TMOD3 after platinum treatment in platinum-sensitive and platinum-resistant ovarian cancers. The Kaplan-Meier method was used to assess the effect of TMOD3 on overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients. microRNAs (miRNAs) targeting TMOD3 were predicted using TargetScan and analyzed using the TCGA database. Tumor Immune Estimation Resource (TIMER) and an integrated repository portal for tumor-immune system interactions (TISIDB) were used to determine the relationship between TMOD3 expression and immune infiltration. TMOD3 coexpression networks in ovarian cancer were explored using LinkedOmics, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and The Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics. The results showed that TMOD3 was highly expressed in ovarian cancer and was associated with the grading, staging, and metastasis of ovarian cancer. TMOD3 expression was significantly reduced in platinum-treated ovarian cancer cells and patients. However, TMOD3 expression was higher in platinum-resistant ovarian cancer cells and tissues compared to platinum-sensitive ones. Higher TMOD3 expression was significantly associated with lower OS and PFS in ovarian cancer patients treated with platinum-based chemotherapy. miRNA-mediated post-transcriptional regulation is likely responsible for high TMOD3 expression in ovarian cancer and platinum-resistant ovarian tissues. The expression of TMOD3 mRNA was associated with immune infiltration in ovarian cancer. These findings indicate that TMOD3 is highly expressed in ovarian cancer and is closely associated with platinum resistance and immune infiltration.

Deep learning has benefits to find complicated interactions between biological entities and could make useful estimation. In clinical practice, the prediction of platinum resistance in ovarian cancer is an important problem because it alters treatment options for patients and subsequently their quality of life. In this paper, Deep Neural Network (DNN) models are designed and evaluated with several feature selection approaches. Among the feature selection approaches, genes selected by group difference in gene expression showed the best performance of 0.838 in test accuracy and 0.889 in test AUC. Hybrid ensemble approaches displayed a performance of 0.903 in test accuracy and 0.869 in test AUC. An alternative hybrid ensemble model with removed partially sensitive samples displayed the performance of 0.903 in test accuracy and 0.914 in test AUC. These results suggest that a hybrid ensemble approach could help prediction of platinum resistance in ovarian cancer and subsequent treatment practice in clinics.

Deep learning has benefits to find complicated interactions between biological entities and could make useful estimation. In clinical practice, the prediction of platinum resistance in ovarian cancer is an important problem because it alters treatment options for patients and subsequently their quality of life. In this paper, Deep Neural Network (DNN) models are designed and evaluated with several feature selection approaches. Among the feature selection approaches, genes selected by group difference in gene expression showed the best performance of 0.838 in test accuracy and 0.889 in test AUC. Hybrid ensemble approaches displayed a performance of 0.903 in test accuracy and 0.869 in test AUC. An alternative hybrid ensemble model with removed partially sensitive samples displayed the performance of 0.903 in test accuracy and 0.914 in test AUC. These results suggest that a hybrid ensemble approach could help prediction of platinum resistance in ovarian cancer and subsequent treatment practice in clinics.

Background/Objectives: This study aimed to determine whether the expression levels of GPAT4 and SLC7A11 are associated with survival outcomes and platinum resistance in epithelial ovarian cancer (EOC) patients. Methods: We analyzed the medical records of EOC patients. EOC samples obtained during surgery were stained for GPAT4 and SLC7A11. Cox regression and Kaplan-Meier analyses were performed to assess the impact of GPAT4 and SLC7A11 expression on overall survival (OS). Results: We found that GPAT4 and SLC7A11 expression levels were greater in platinum-resistant ovarian cancer tissues than in platinum-sensitive ovarian cancer tissues. High expression of both GPAT4 and SLC7A11 was associated with an increased risk of platinum resistance compared with low expression of both factors. High expression of both SLC7A11 and GPAT4 was independently correlated with poor OS, highlighting the significance of this integrated metric as a prognostic factor in ovarian cancer. The GPAT inhibitor (GPAT-IN-1) and an SLC7A11 inhibitor (erastin) attenuated platinum resistance in ovarian cancer cells, and their combined application increased cytotoxicity. Furthermore, the combination of GPAT-IN-1, erastin, and cisplatin significantly improved the chemotherapeutic effects on platinum-resistant ovarian cancer cells. Conclusions: High expression of both SLC7A11 and GPAT4 is related to platinum resistance in EOC patients. The high expression of both SLC7A11 and GPAT4 serves as an important independent prognostic factor and indicates potential therapeutic targets for patients with platinum-resistant EOC.

<div>Abstract<p>Ovarian cancer remains one of the deadliest gynecologic malignancies affecting women, and development of resistance to platinum remains a major barrier to achieving a cure. Multiple mechanisms have been identified to confer platinum resistance. Numerous miRNAs have been linked to platinum sensitivity and resistance in ovarian cancer. miRNA activity occurs mainly when the guide strand of the miRNA, with its seed sequence at position 2–7/8, is loaded into the RNA-induced silencing complex (RISC) and targets complementary short seed matches in the 3′ untranslated region of mRNAs. Toxic 6mer seeds, which target genes critical for cancer cell survival, have been found in tumor-suppressive miRNAs. Many siRNAs and short hairpin RNAs (shRNA) can also kill cancer cells via toxic seeds, the most toxic of which carry G-rich 6mer seed sequences. We showed here that treatment of ovarian cancer cells with platinum led to increased RISC-bound miRNAs carrying toxic 6mer seeds and decreased miRNAs with nontoxic seeds. Platinum-tolerant cells did not exhibit this toxicity shift but retained sensitivity to cell death mediated by siRNAs carrying toxic 6mer seeds. Analysis of RISC-bound miRNAs in tumors from patients with ovarian cancer revealed that the ratio between miRNAs with toxic versus nontoxic seeds was predictive of treatment outcome. Application of the 6mer seed toxicity concept to cancer relevant miRNAs provides a new framework for understanding and predicting cancer therapy responses.</p>Significance:<p>These findings demonstrate that the balance of miRNAs that carry toxic and nontoxic 6mer seeds contributes to platinum resistance in ovarian cancer.</p></div>

<div>Abstract<p>Ovarian cancer remains one of the deadliest gynecologic malignancies affecting women, and development of resistance to platinum remains a major barrier to achieving a cure. Multiple mechanisms have been identified to confer platinum resistance. Numerous miRNAs have been linked to platinum sensitivity and resistance in ovarian cancer. miRNA activity occurs mainly when the guide strand of the miRNA, with its seed sequence at position 2–7/8, is loaded into the RNA-induced silencing complex (RISC) and targets complementary short seed matches in the 3′ untranslated region of mRNAs. Toxic 6mer seeds, which target genes critical for cancer cell survival, have been found in tumor-suppressive miRNAs. Many siRNAs and short hairpin RNAs (shRNA) can also kill cancer cells via toxic seeds, the most toxic of which carry G-rich 6mer seed sequences. We showed here that treatment of ovarian cancer cells with platinum led to increased RISC-bound miRNAs carrying toxic 6mer seeds and decreased miRNAs with nontoxic seeds. Platinum-tolerant cells did not exhibit this toxicity shift but retained sensitivity to cell death mediated by siRNAs carrying toxic 6mer seeds. Analysis of RISC-bound miRNAs in tumors from patients with ovarian cancer revealed that the ratio between miRNAs with toxic versus nontoxic seeds was predictive of treatment outcome. Application of the 6mer seed toxicity concept to cancer relevant miRNAs provides a new framework for understanding and predicting cancer therapy responses.</p>Significance:<p>These findings demonstrate that the balance of miRNAs that carry toxic and nontoxic 6mer seeds contributes to platinum resistance in ovarian cancer.</p></div>

Ovarian cancer remains one of the deadliest gynecologic malignancies affecting women, and development of resistance to platinum remains a major barrier to achieving a cure. Multiple mechanisms have been identified to confer platinum resistance. Numerous miRNAs have been linked to platinum sensitivity and resistance in ovarian cancer. miRNA activity occurs mainly when the guide strand of the miRNA, with its seed sequence at position 2-7/8, is loaded into the RNA-induced silencing complex (RISC) and targets complementary short seed matches in the 3' untranslated region of mRNAs. Toxic 6mer seeds, which target genes critical for cancer cell survival, have been found in tumor-suppressive miRNAs. Many siRNAs and short hairpin RNAs (shRNA) can also kill cancer cells via toxic seeds, the most toxic of which carry G-rich 6mer seed sequences. We showed here that treatment of ovarian cancer cells with platinum led to increased RISC-bound miRNAs carrying toxic 6mer seeds and decreased miRNAs with nontoxic seeds. Platinum-tolerant cells did not exhibit this toxicity shift but retained sensitivity to cell death mediated by siRNAs carrying toxic 6mer seeds. Analysis of RISC-bound miRNAs in tumors from patients with ovarian cancer revealed that the ratio between miRNAs with toxic versus nontoxic seeds was predictive of treatment outcome. Application of the 6mer seed toxicity concept to cancer relevant miRNAs provides a new framework for understanding and predicting cancer therapy responses. SIGNIFICANCE: These findings demonstrate that the balance of miRNAs that carry toxic and nontoxic 6mer seeds contributes to platinum resistance in ovarian cancer.

Platinum resistance is a major barrier to the effective treatment of advanced-stage ovarian cancer; however, factors leading to the development of resistance are not well understood. In fact, the role of environmental endocrine disrupting chemicals, such as perfluoroalkyl substances (PFAS), have seldom been explored. This is important because select PFAS have been linked to adverse reproductive outcomes in females including endometriosis, oocyte apoptosis, infertility, and increased even ovarian cancer risk at very high exposure levels. The relationship between PFAS and adverse female reproductive outcomes, as well as reports of other endocrine disruptors leading to therapy resistance, led, in the current study, to the evaluation of the effect of PFAS exposure on response to carboplatin in ovarian cancer cells. We recently showed that select PFAS, at human-relevant concentrations, induced carboplatin resistance in OVCAR-3 and Caov-3 cells; however, the mechanism underlying the onset of resistance remains largely unknown. Since platinum-resistant ovarian cancer is characterized, in part, by increased mitochondrial networks and enhanced bioenergetic capacities, the central hypothesis of this study is that PFAS induce alterations to mitochondrial biology. Mitochondrial endpoints of interest included redox ratio and superoxide production. To measure redox ratio, nicotinamide dinucleotide (NADH) and flavin adenine dinucleotide (FAD), which are inherently fluorescent, were measured using a fluorescence plate reader. Since NADH and FAD are metabolites produced via oxidative phosphorylation and glycolysis, evaluating redox ratio can provide an understanding of which pathway is preferred in the presence of environmental stimuli like PFAS. In OVCAR-3 and Caov-3 cells, baseline NADH:FAD ratios were 3.3 and 3.5, respectively. After 48 hours of PFAS exposure, NADH:FAD ratios of OVCAR-3 and Caov-3 cells ranged from 8-10 or 6-10, respectively. This increase after PFAS exposure could suggest enhanced energy production capabilities that warrant further investigation. As an additional measure, superoxide production was measured using flow cytometry. OVCAR-3 and Caov-3 cells were exposed to PFAS for 6 days prior to isolating cell pellets and incubating them with MitoSOX (mitochondrial) and SYTOX Blue (nuclear) dyes. After 15–30-minute incubations, samples were run on the flow cytometer. Compared to controls, superoxide production in PFAS-exposed ovarian cancer cells increased by up to 200%. Often, cancer cells have elevated levels of reactive oxygen species due to enhanced energy production and signaling pathways, thus this finding further suggests that PFAS affect mitochondrial energy pathways. Altogether, these data show that PFAS exposure, which can induce carboplatin resistance in OVCAR-3 and Caov-3 cells, increases redox ratios and superoxide production in ovarian cancer cells. Therefore, targeting alterations in mitochondrial biology arising from PFAS exposure using precision medicine could be effective in overcoming platinum resistance in ovarian cancer. Citation Format: Brittany P. Rickard, Marta Overchuk, Vesna A. Chappell, Carl D. Bortner, Victoria L. Bae-Jump, Suzanne E. Fenton, Imran Rizvi. Perfluoroalkyl substances (PFAS) induce platinum resistance in ovarian cancer through altering mitochondrial function [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B100.

Platinum resistance remains a significant obstacle in the treatment of advanced-stage ovarian cancer, frequently leading to therapeutic failure. Our previous research identified Superoxide Dismutase 1 (SOD1) as a key antioxidant target for re-sensitizing platinum-resistant ovarian cancer cells to platinum-based therapies through both enzymatic inhibition and RNA interference (RNAi) utilizing a graphene-based siRNA delivery platform. Building on these findings, we have now developed a liposomal formulation of chemically modified siRNA targeting SOD1, which demonstrates potent knockdown efficiency and significantly enhances the sensitivity of resistant ovarian cancer cells to cisplatin in vivo. While SOD1 inhibition or knockdown via RNAi effectively re-sensitizes resistant cells to cisplatin, the underlying redox-sensitive signaling pathways remain largely unexplored in ovarian cancer. Our current study reveals that SOD1 knockdown acts as a redox switch, triggering cellular reprogramming in drug-resistant cells through post-translational cysteine modifications. This reprogramming leads to the rewiring of critical cancer hallmarks, culminating in the restoration of a cisplatin-sensitive phenotype. These findings suggest that a liposomal, chemically modified SOD1 siRNA formulation could serve as a promising therapeutic approach for reversing platinum resistance in ovarian cancer by exploiting redox-mediated reprogramming of cancer hallmarks. This study not only underscores the therapeutic potential of targeting SOD1 but also highlights the broader implications of redox signaling in the etiology of platinum resistance, providing a novel avenue for therapeutic intervention. Citation Format: Attila Szenasi, Sonia Rocha, Mu Wang. Redox reprogramming by SOD1 knockdown: A novel liposomal siRNA strategy to overcome platinum resistance in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B025.

PurposeOvarian cancer is one of the common malignant tumors of female reproductive organs, which seriously threatens the life and health of women. Resistance to chemotherapeutic drugs for ovarian cancer is the root cause of recurrence in most patients. The purpose of this study is to determine the differentially expressed genes of platinum resistance in ovarian cancer, and to screen out molecular targets and diagnostic markers that could be used to treat ovarian cancer platinum resistance.MethodsWe downloaded 5 gene microarray datasets GSE58470, GSE45553, GSE41499, GSE33482, and GSE15372 from the Gene Expression Omnibus database, all of which are associated with ovarian cancer platinum resistance. Subsequently, the intersection of the statistically significant differentially expressed genes in 5 gene chips was taken, and relevant bioinformatics and clinical parameters were performed on the screened differential genes. qRT-PCR was utilized to examine the mRNA expression levels in ovarian cancer sensitive and cisplatin-resistant cells.ResultsThree differential genes, IFI27, JAG1, DNM3, may be closely related to platinum resistance of ovarian cancer, were screened by microarray datasets. According to the combined verification of bioinformatics, clinical case analyses and experiments, it was inferred that the increased expression of DNM3 was beneficial to patients with platinum resistance, but the high expression of IFI27 and JAG1 may lead to the risk of platinum resistance.ConclusionIFI27, JAG1 and DNM3 screened by relevant gene chips may serve as new biomarkers of platinum resistance in ovarian cancer.

Purpose: The objective of this investigation was to evaluate the preclinical activity of MLN4924, an investigational inhibitor of the NEDD8-activating enzyme, against chemoresistant and chemosensitive ovarian cancer cells. ExperimentalDesign: Efficacy of MLN4924 both alone and in combination with cisplatin was assessed using short-term tetrazolium based and longer term focus formation assays. Mechanistic studies included cell cycle analysis, evaluation of DNA-platinum adduct formation (using an ELISA), and evaluation of DNA damage repair pathways. In addition, we employed an siRNA screen to assess the contribution of each member of the Cullin RING-Ligase (CRL) family of E3 ubiquitin ligases, the best characterized downstream mediators of MLN4924’s biological effects. Results: Single agent MLN4924 exhibited moderate activity in ovarian cancer cell lines. The combination of MLN4924 with cisplatin or carboplatin resulted in significant platinum sensitization in SKOV3 and ES2 cells, as well as, in several primary ovarian cancer cell lines established from high grade serous, clear cell, and serous borderline ovarian tumors. Furthermore, the platinum sensitizing effect of MLN4924 was also observed in several in vitro models of platinum resistant ovarian cancer (using both established and primary chemoresistant ovarian cancer cells). Mechanistically, we show that depletion of CUL3 and CUL5 augment, while knockdown of CUL1 and CUL4A antagonize cisplatin-induced cytotoxicity in ovarian cancer cells. The combination of cisplatin and MLN4924 was not associated with DNA re-replication, altered platinum-DNA adduct formation, or abrogation of FANCD2 monoubiquitination. Conclusions: Our investigation reveals a novel mechanism for overcoming platinum resistance in vitro, and provides a strong rationale for clinical investigations of platinum and MLN4924 combinations in ovarian cancer. This work also highlights that different CRL ubiquitination pathways can have distinct and opposing effects on platinum sensitivity and resistance in ovarian cancer cells. Citation Format: Amir A. Jazaeri, Etsuko Shibata, Jonghoon Park, Jennifer Bryant, Mark R. Conaway, Susan C. Modesitt, Peter G. Smith, Michael Milhollen, Allison J. Berger, Anindya Dutta. Overcoming platinum resistance in ovarian cancer using the novel compound MLN4924. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3380. doi:10.1158/1538-7445.AM2013-3380

ObjectiveThe need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinum-based chemotherapy in ovarian cancer.MethodsWe enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively.ResultsNLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P<0.001, <0.001, 0.029, and <0.001, respectively). The Kaplan-Meier curves revealed that high LDH level (≥250 U/L) was associated with reduced PFI (P=0.037 and 0.012) and DFS (P=0.007 and 0.002) in groups A and B, respectively. High NLR (≥4) was associated with reduced DFS in both groups (P=0.036 and 0.005, respectively). LDH showed higher area under the curve (AUC) values in predicting platinum resistance with a PFI of less than 6 months and 12 months (AUC=0.606 and 0.646, respectively) than NLR. In the multivariate analysis, LDH remained significant (P=0.019) after adjusting for the 9 blood parameters.ConclusionSerum LDH level may possibly predict platinum resistance and prognosis in ovarian cancer and may be useful when developing precision medicine for individual patients.