Among gynecological cancers, epithelial ovarian cancer (EOC) stands out with the highest mortality rate. Each year, nearly 295,000 females are diagnosed with EOC worldwide, and 185,000 die from this disease [1]. EOC is the main cause of cancer deaths among women in the United States and accounts for the first death of gynecological cancer [2, 3]. The mortality due to EOC is attributed primarily to the difficulty in its early detection and its resistance to treatment. Approximately 70% of patients with EOC are diagnosed as the International Federation of Gynecology and Obstetrics (FIGO) stage III or stage IV when their disease is identified [4]. Despite the use of radical first-line treatment, 70% of patients with EOC will experience a relapse in the first 3 years postdiagnosis.

Study of the mechanisms that underlie tumor progression have shown that some immune cells are part of the cell composition of the tumor microenvironment, playing crucial roles in tumor invasion including proliferation, evolution, and diffusion [5]. It has also been demonstrated that the immune/inflammatory cell composition is correlated with the tumorigenesis, development, and diffusion of EOC. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) were shown to be significance prognosis indicators in non-small-cell lung cancer, digestive-system tumors, and EOC [6, 7, 8, 9, 10].

Onodera’s prognostic nutritional index (OPNI) has been used to assess patients with digestive-system tumors; the OPNI = serum albumin (g/L) + 5 $\times$ lymphocyte count (10${}^9$/L) [11], and the OPNI was demonstrated to be a useful prognostic index in many digestive-system malignancies [12, 13, 14, 15]. The prognostic significance of the OPNI for serous ovary cancer (SOC) has not been known. We conducted the present study to assess the prognostic value of the OPNI, the NLR, the PLR, and the systemic immune-inflammatory index (SII) for serous ovary cancer.

Serous ovarian carcinoma (SOC) is a highly malignant disease, presenting ascites, hypoproteinemia, and subsequently malnutrition. When tumor cells cannot obtain the nutrition they require from their host’s body, the body’s destruction will be accelerated. Patients’ nutritional evaluations thus play a crucial role in the prediction of disease progression. As emphasized by Thompson et al. [17], the immune system plays a crucial role in aggravating the progression of a tumor.

The OPNI, which was first applied in 1984, can be used to evaluate the risk of post-surgery complications and mortality in individuals with gastrointestinal tumors, and the OPNI has been gradually used to assess the survival of various carcinoma types, especially digestive-system tumors [18, 19]. In our two-center retrospective research, we discovered that patients with SOC and a high OPNI value achieved better OS. In the present study’s univariate and multivariate survival analyses, the OPNI was a better independent prognostic marker compared to the NLR, PLR, and SII, which are important parameters representing both inflammatory and nutritional status.

Another study indicated that the OPNI is associated with nutritional and immune status [20], which led us to speculate that the OPNI might be potential prognostic marker in OC. Study has suggested that the OPNI holds potential for predicting postoperative complications and the duration of hospital stays in patients with esophageal carcinoma [21]. Additionally, a low OPNI score may adversely affect the OS of these patients [21]. Xu et al. [22] revealed that the OPNI had high utility in the prediction of the survival of patients with hepatocellular carcinoma; their analyses demonstrated that the patients with high OPNI scores had better OS. Wang et al. [23] reported that low OPNI scores were associated with worse recurrence-free survival (RFS), suggesting that the OPNI could be used as an independent prognostic marker for gastrointestinal stromal tumors.

The distribution of clinical characteristics, OS, and progression-free survival (PFS) of patients with metastatic non-small cell lung cancer were clearly different in the group of patients with high OPNI scores compared to those of the group of patients with low OPNI scores in a study by Bozkaya et al. [24]. Our present investigation revealed correlations between the OPNI and the clinicopathological characteristics of patients with SOC. We observed that the patients’ tumor stage, NLR, PLR, SII, and OPNI values were clearly associated with the overall survival of SOC patients in a univariate survival analysis. Although the NLR, PLR, and SII were not identified as independent prognostic markers for OS in our multivariate analyses, the OPNI was identified as such a marker and was closely related to the prognosis of serous ovarian cancer.

Most women with advanced ovarian cancer need repeated drainage for ascites, with a high amount of protein leakage. Protein loss often leads to patients’ malnutrition. It is thus understandable that low OPNI scores were observed to be associated with advanced-stage SOC cases in the present study. In addition, higher rates of postsurgery complications and mortality were documented in patients with malnutrition [25]. A reduction in serum albumin levels indicates a compromised nutritional status, signifying a state of malnutrition. A decline in nutritional well-being is directly proportional to weakened immunity, consequently contributing to the progression of disease [26]. Nutrition-support treatment can effectively improve the prognosis of cancer patients [27]. We thus propose that the OPNI should be applied routinely in clinical settings for predicting the prognoses of patients with cancer.

The PLR value reflects the body’s balance of inflammatory and immune responses and has been widely studied in cancer research. The PLR values of lung cancer patients are significantly higher than those of healthy individuals. Similarly, in a study comparing benign ovarian tumors with ovarian cancer, the PLR was significantly elevated in the malignant cases [28]. A meta-analysis revealed that among patients with ovarian cancer, having an elevated PLR was associated with significantly reduced OS, and the PLR could be used as an independent predictor of prognosis in ovarian cancer. Our present findings demonstrated that the PLR had a significant prognostic value for SOC in a univariate analysis and the high-PLR group (PLR $\ge$224.4) had poorer OS, whereas in our multivariate survival analysis the PLR was not an independent prognostic factor for OS.

The systemic immune-inflammation index (SII) is a novel inflammatory marker that incorporates neutrophil, platelet, and lymphocyte counts. Emerging research has shown that the SII holds promise in predicting the prognosis of various tumors, including lung, gastric, and esophageal cancers; the SII value is also believed to accurately reflect inflammatory status. The utility of the SII has been widely studied in cancer research [29, 30]. The SII is the ratio of platelets multiplied by the neutrophil and lymphocyte counts, and an elevated SII indicates a relative increase in the platelet and/or neutrophil counts or a relative decrease in the lymphocyte count. Platelets play a crucial role in the recruitment of neutrophils and macrophages to the tumor microenvironment, and increased platelet counts in the peripheral blood correlate with poor tumor prognosis. In ovarian cancer, it has been shown that the FIGO stage in high-SII patients was significantly later and more prone to lymph node metastasis compared to low-SII patients, and that low-SII patients had longer PFS and OS compared to high-SII patients.

The results of our present investigation demonstrated that the SII had a significant prognostic value for OS in the univariate analysis, and the low-SII group (SII 747.4) achieved superior OS. The SII values were negatively correlated with the prognosis of the malignant tumors.

Neutrophils play a crucial role in tumor development and progression, being mechanistically attracted to the tumor microenvironment. Once there, they release factors that promote proliferation and inhibit T-lymphocyte activity, thus facilitating tumor angiogenesis, invasion, and metastasis [31, 32, 33, 34]. The neutrophil-to-lymphocyte ratio (NLR) acts as a reliable gauge of systemic inflammation, capturing the delicate balance between anti-tumor immune activity and pro-tumor inflammation. Moreover, NLR stands out as an autonomous prognostic indicator across a spectrum of malignancies [35, 36, 37, 38]. Kwon et al. [39] discovered a correlation between an elevated NLR and lymph node metastasis, ascites, and FIGO staging in ovarian cancer patients. Moreover, ovarian cancer patients with a high NLR experienced shortened PFS and an increased mortality rate.

An increasing number of studies have pointed out that the NLR is related to the diagnosis of patients with early-stage ovarian cancer, and some studies combined the NLR and CA-125 to explore the significance of the NLR in the diagnosis of ovarian cancer [40, 41]. The results of those studies revealed that the combined use of the NLR and CA-125 can increase the detection rate of early-stage ovarian cancer. Another study suggested that ovarian cancer patients with an elevated NLR are more prone to progress to an advanced stage, and the risks of metastasis and recurrence were also increased in these patients [42]. The results of these studies affirm that a heightened NLR is an important observation in the monitoring of ovarian cancer’s progression.

There are some study limitations to address. We did not obtain the patients’ progression-free survival data. In addition, since this was not a prospective study, the results could have been affected by unfounded clinical characteristics. Multi-center prospective studies with greater numbers of patients could help overcome these limitations.

Our data showed that the OPNI, NLR, PLR and SII can be used broadly as effective indices to assist the prognostic assessment of patients with serous ovarian cancer. Additionally, OPNI is the only independent prognostic indicator for SOC patients in our study. The applications and practical value of the OPNI, NLR, PLR and SII in clinical settings merit further investigation.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

LZ and WH contributed to the study’s conception and design. YH designed the study, wrote the manuscript text, and analyzed the data. Material preparation, data collection, and statistical analysis was performed by JG. Data collection was performed by WL and YS, FY, XZ, and KX. All authors revised the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Changzhi People’s Hospital (Changzhi, China; No. 2024K009), and Yuncheng Central Hospital (Yuncheng, China; YXLL2022011-4).

Thanks for the gynecology colleagues of the Changzhi People’s Hospital and Yuncheng Central Hospital.

This research received no external funding.

The authors declare no conflict of interest.