<p>Mediation Analysis Reveals Potential Biological Mechanism of Ascites Influencing Recurrence in Patients with Epithelial Ovarian Cancer</p>

Abstract

Objective: Ascites, an accumulation of peritoneal fluid, is associated with poor prognosis of certain cancers. The potential mechanism that ascites worsens prognosis has not been well understood. Lipids have been reported to correlate with the prognosis of patients with epithelial ovarian cancer (EOC). Therefore, we aimed here to investigate whether lipids mediate the effect of ascites on the recurrence of EOC. Methods: We collected the demographic and pathological data of 437 previously untreated patients with EOC to investigate the influence of ascites on recurrence. To identify the mechanism that mediates the potential influence of ascites on recurrence, we used ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) to determine the plasma lipid profiles of 53 patients with EOC. We used mediation analysis to evaluate if lipids mediated the effects of ascites on the recurrence of EOC. Results: Patients with ascites had a poorer prognosis, which was associated with higher levels of carbohydrate antigen-CA125 (CA125) and FIGO stage. We identified six different lipid metabolites that were associated with ascites and recurrence. Mediation analysis revealed that the lipids LysoPC(P-15:0), PC(P-34:4), and PC(38:6) may mediate the effects of ascites on recurrence. Conclusion: Our findings suggest that LysoPC(P-15:0), PC(P-34:4), and PC(38:6) mediate the effect of ascites on the prognosis of patients with EOC. We believe therefore that it is reasonable to consider metabolic interventions targeting the metabolism of LysoPC(P-15:0), PC(P-34:4), and PC(38:6) as a palliative treatment for patients with EOC with ascites. Further studies of more patients will be required to validate our findings.

Prognostic potential of lipid profiling in cancer patients: a systematic review of mass spectrometry-based studies

“…The number of studies reported for each country is as follows (Fig. 4 b): 10 studies (26%) were reported from China [ 24 , 26 , 28 , 45 , 46 , 50 , 52 , 55 , 59 , 60 ], eight (21%) from Japan [ 31 , 37 – 39 , 41 – 43 , 53 ], four (11%) from the USA [ 30 , 33 , 47 , 48 ], two (5%) each from Australia [ 32 , 34 ], Brazil [ 29 , 61 ], and Germany [ 25 , 40 ], one (3%) each from Argentina [ 54 ], Canada [ 57 ], Czech [ 51 ], Finland [ 44 ], Italy [ 56 ], Netherlands [ 49 ], Portugal [ 36 ], Romania [ 27 ], Singapore [ 58 ], and Spain [ 35 ].…”

“…There were also two cases (5%) [ 36 , 60 ] where the details were not specified in the text. Within the software category, Analyst was the most frequently used in five cases (24%) [ 26 , 30 , 44 , 56 , 61 ], followed by Mass Hunter Qualitative Analysis in three cases (14%) [ 45 , 46 , 51 ]. ALEX [ 25 , 51 ], Metabolon [ 47 , 57 ], MS-DIAL [ 28 , 52 ], Progenesis QI [ 54 , 55 ] and LipidSearch [ 33 , 59 ] were used each in two cases (10%).…”

“…5 a), 33 studies included fewer than 160 cases, demonstrating a bias in the distribution of case numbers. In comparison, only five studies exceeded 160 cases [ 26 , 32 , 44 , 45 , 51 ]. Regarding the breakdown by cancer type, the cancer types with studies involving more than 100 cases were colorectal cancer, prostate cancer, breast cancer, ovarian cancer, bladder cancer, pancreatic cancer, liver cancer, nasopharyngeal carcinoma, and oral cancer.…”

Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites

“…Pelvic-peritoneal cavity transcoelomic route is regarded as the typical way of EOC metastasis, which is widely believed to occur via peritoneal circulation of ascites [ 3 ]. Malignant ascites was a common complication of EOC and was reported to be an independent unfavorable prognostic factor of EOC [ 4 , 5 ]. Constant Malignant ascites led to metastasis [ 6 – 8 ], while the underlying mechanism needs more thorough investigation.…”

Hsa_circ_0000497 and hsa_circ_0000918 contributed to peritoneal metastasis of ovarian cancer via ascites

“…Pelvic-peritoneal cavity transcoelomic route is regarded as the typical way of EOC metastasis, which is widely believed to occur via peritoneal circulation of ascites (3). Malignant ascites was a common complication of EOC and was reported to be an independent unfavorable prognostic factor of EOC (4,5). Constant Malignant ascites led to metastasis (6-8), while the underlying mechanism needs more thorough investigation.…”