1. Introduction
Cervical cancer is a malignant tumour that seriously threatens the life and health of women. Cervical cancer has the second highest occurrence rate (second to breast cancer) among female malignant tumours [
1]. Women aged 40–60 years are more likely to develop cervical cancer, although there has been trend towards younger ages [
2]. Currently, surgery is one of the primary methods for treating cervical cancer; however, the postoperative overall survival (OS) rate remains unsatisfactory, and postoperative treatment is mostly supplemented with radiotherapy and chemotherapy to prolong patient survival [
3]. However, disease recurrence and progression result in the death of approximately one-third of the patients each year [
4]. Therefore, exploring the biological mechanisms of cervical cancer progression and the influencing factors of prognosis is essential. Recent studies have demonstrated that cervical cancer is closely associated with the body’s inflammatory response and nutritional status [
5,
6]. The platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) are valid indicators that reflect the systemic inflammatory response and nutritional status [
7,
8]. Reportedly, PLR and PNI affect the treatment efficacy and prognosis of various malignancies, such as ovarian cancer, gastric cancer, oesophageal cancer, and breast cancer [
9,
10,
11,
12]. The higher the PLR and the lower the PNI, the higher the risk of malignant tumour progression and metastasis, thus resulting in poor patient prognosis. Age, tumour size, clinical stage, and lymph node metastasis are factors affecting cervical cancer prognosis [
13,
14]. Few reports exist on the relationship between PLR, PNI, and the prognosis of patients with cervical cancer who received radiotherapy. Herein, we analysed the potential applicability of PLR and PNI in the prognostic evaluation of cervical cancer by comparing the clinical characteristics, efficacy, and survival differences of patients with cervical cancer in various pre-treatment PLR and PNI groups.
4. Discussion
It has been reported that over 80% of the newly diagnosed cases of cervical cancer occur in developing countries each year, where the disease is characterized by high incidence and mortality rates [
16]. This significantly increases the economic burden on patients’ families and society. Therefore, it is of great importance to effectively predict prognosis and provide personalized interventions to improve patient outcomes and enhance their quality of life [
17]. Currently, factors such as the cancer stage, lymph node metastasis, pathological type, and degree of tumour differentiation are clinically used to evaluate the prognosis of patients [
18]. However, except for a few factors, such as staging, that can be evaluated before treatment, most of the other factors can only be evaluated after treatment. In addition, the ribonucleic acid and human papillomavirus expressions have also been demonstrated to serve as factors for the prognostic assessment of patients with cervical cancer [
10,
19]; however, their clinical applicability is limited because they are expensive and challenging to detect. The prognosis of patients depends on discovering a predictive indicator that can be assessed prior to radiotherapy and is convenient to detect. The study of tumour development, invasion, and metastasis in relation to genomics and proteomics has continued to advance in recent years [
20]. Researchers have gradually discovered that the body’s nutritional status, the level of the systemic inflammatory response, and the immune regulatory mechanisms might affect the processes of tumour development, invasion, and metastasis to some extent. Clinical attention to PNI and PLR has been growing as a result of ongoing research on immune-nutritional indicators of malignant tumours.
Onodera et al. [
21] first introduced the PNI. Serological albumin levels and lymphocyte counts, both of which use indicators that indirectly reflect the nutritional status and the immune performance of the patient to some extent, are used to evaluate this index [
12]. The PNI is an objective and simple assessment tool that is easily accessible non-invasive. Serum albumin is one of the most important clinical indicators for assessing a patient’s nutritional status. Several studies have demonstrated that low serum albumin levels are associated with a poor prognosis in patients with various cancers [
22]. Graziano et al. [
23] retrospectively analysed the serum albumin levels of 2425 patients with non-metastatic invasive breast cancer (stages I–III) and reported that lower serum albumin levels served as a prognostic factor for poor survival in patients with early stage breast cancer, regardless of their stage. When patients with cervical cancer are malnourished, the postoperative recovery is poor, the body’s immunity and resistance are affected by varying degrees, the treatment tolerance is poor, and the risk of postoperative recurrence or disease progression is high, resulting in poor prognosis. Ida et al. [
24] found that pre-treatment low PNI values were significantly associated with poorer OS in cervical cancer patient compared to those with high PNI values. Moreover, low PNI values were indicative of malnutrition in recurrent cervical cancer patients. Lymphocytes play a crucial role in the body’s immune response function, which can reflect the body’s immune, nutritional, and inflammatory response status [
20,
25]. When lymphocyte levels are normal, cytotoxic lymphocyte proliferation activation can effectively inhibit malignant tumour cell proliferation or migration and prevent cervical cancer progression or recurrence, thereby improving patient prognosis. Therefore, PNI can reflect a patient’s nutritional status and immune function, and its role in assessing the efficacy and prognosis has gained increasing attention. Xiao et al. [
26] retrospectively analysed 193 patients with oesophageal cancer who received radical radiotherapy and demonstrated that the OS rate was higher in the high PNI group than in the low PNI group. Haraga et al. [
27] reported that reduced PNI values were an independent poor prognostic factor for a patient’s OS and PFS through a study of patients with cervical cancer who received synchronous radiotherapy.
Non-specific inflammatory responses play an extremely important role in the progression of tumours. This may be because inflammatory factors release large amounts of reactive oxygen species and proteases, causing DNA oxidative damage in cells, ultimately triggering tumours [
28]. PLR is a common haematological indicator reflecting the systemic inflammatory response obtained from the platelet-to-lymphocyte ratio [
29]. Platelets are part of the inflammatory response, with reactive thrombocytosis being more common in solid tumours. Platelets can release various factors, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta (TGF-β). These factors can promote the proliferation and adhesion of malignant tumour cells, thus affecting tumour growth and metastasis [
30]. Thrombocytosis and lymphopenia are associated with the host’s degree of systemic inflammatory response. An elevated PLR indicates a relative increase in the platelet count or a relative decrease in the lymphocyte count. Several studies have demonstrated that PLR can be used not only as an indicator for the evaluation of immune function status but also as a poor prognostic factor for various malignant tumours [
31].A retrospective study of 389 patients with advanced non-small cell lung cancer reported that a PLR below the cut-off value was associated with a longer PFS (
p = 0.028) and OS (
p = 0.001) and a higher objective response rate (
p = 0.04) [
32]. Raungkaewmanee et al. [
9] demonstrated that pre-treatment PLR was associated with prognosis in epithelial ovarian cancer, with a lower survival rate and PFS observed in the high PLR group. Ma et al. [
33] performed a meta-analysis of 3668 patients with cervical cancer and demonstrated that elevated pre-treatment PLR was associated with poorer OS and could be used as a biological marker for poor prognosis in patients with cervical cancer.
Herein, we retrospectively analysed 110 patients with cervical cancer who received radiotherapy and were divided into the high PLR, low PLR, high PNI, and low PNI groups. Significant differences were observed in terms of the age and prognosis between the high PNI and low PNI groups (p < 0.05), while significant differences were observed in terms of the histological type, lymph node metastasis, and prognosis between the high PLR and low PLR groups (p < 0.05). This reflects the role of PNI and PLR in tumour formation and suggests a link between PLR and PNI and tumour progression. When the relationship between PNI, PLR, and prognosis was further explored, we observed that the 3-year OS and PFS were significantly higher in the high PNI group than in the low PNI group (p < 0.05), and 3-year OS and PFS were significantly higher in the low PLR group than in the high PLR group (p < 0.05). PNI and PLR were found to be independent influencing factors on OS based on multifactorial Cox regression analysis (p < 0.05). However, PNI and PLR were not independent influencing factors for PFS (p > 0.05). This indicates that higher pre-treatment PNI values or lower pre-treatment PLR values were associated with better OS for patients. Nevertheless, the predictive value of PNI and PLR on PFS requires further study.
However, our study has certain limitations. First, the sample size of this study was small, and its retrospective single-centre design might have introduced some potential bias. Second, the patient survival varied widely, ranging from 1 to 4 years after diagnosis. Therefore, the survival analysis results might be biased. Third, the serial PNI or PLR counts for each patient during concurrent radiotherapy or radiotherapy alone were lacking. As a dynamic marker, the continuous measurement of PNI or PLR during treatment can potentially help in the early identification of patients who will not benefit from a single treatment. Changes in the PLR need to be further evaluated by clinical trials wherein the data can be prospectively analysed. Fourth, there is still no consensus on the optimal PNI and PLR cut-off values. Some studies used the median value to define the cut-off value, whereas some studies used the ROC curve. Our findings require more scientific evidence, which should come from prospective multicentre trials with larger sample sizes.
In summary, preoperative peripheral blood PNI and PLR could serve as predictive indicators for evaluating the curative effect and prognosis of patients with cervical cancer. Low PNI and high PLR indicate poor prognosis. At the same time, both indicators are easy to detect and will not increase the economic burden on patients. These indicators are expected to serve as clinical parameters for predicting the efficacy and prognosis of radiotherapy in patients with early stage cervical cancer, thus guiding clinical decision making.