Abstract

Background:

To study the correlation between the expression of immune factors and the prognosis of surgical treatment of plasma cell mastitis (PCM) and to analyze its predictive value for the prognosis of patients.

Methods:

89 female patients with PCM treated in our hospital from June 2020 to September 2022 were divided into good prognosis group (69 cases) and poor prognosis group (20 cases). Logistic regression was used to analyze the influencing factors of poor prognosis of surgical treatment for PCM, and to explore the correlation between these immune factors and the prognosis of surgical treatment for PCM. Draw the receiver operating characteristic (ROC) curve to analyze the predictive value of the above indexes for the prognosis of patients with PCM.

Results:

After 4 weeks of treatment, the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were significantly lower than before treatment (p < 0.05), and the level of interleukin 10 (IL-10) was significantly higher than before treatment (p < 0.05). At the time of admission, there was no significant difference in the clinical data and the levels of TNF-α, IL-6 and IL-10 between the two groups (p > 0.05). After 4 weeks of treatment, the indexes of TNF-α and IL-6 in the poor prognosis group were higher than those in the good prognosis group (p < 0.05). Logistic regression analysis showed that the levels of TNF-α (odds ratio (OR) = 1.551, 95% confidence interval (95% CI): 1.276–1.886) and IL-6 (OR = 1.082, 95% CI: 1.046–1.119) were increased, which were risk factors for the prognosis of PCM (OR >1). Correlation analysis showed that TNF-α and IL-6 were negatively correlated with the prognosis of PCM, while IL-10 was positively correlated with the prognosis of PCM. ROC curve analysis showed that the areas under the curve for TNF-α, IL-6 and IL-10 to predict the prognosis of surgical treatment of PCM were 0.896, 0.931 and 0.709 respectively.

Conclusions:

The expression of immune factors such as TNF-α, IL-6 and IL-10 is closely related to the prognosis of surgical treatment of PCM, which has high predictive value for its prognosis.

1. Introduction

Plasma cell mastitis (PCM) is a rare inflammatory breast disease, which is characterized by the infiltration of a large number of plasma cells in breast tissue. The disease is usually manifested by breast mass, pain or body temperature discomfort [1]. Although the pathogenesis is not fully understood, factors such as abnormal immune system and autoimmune diseases are considered to be related to this. Because of the complexity of its pathogenesis, the diagnosis and treatment of the disease face many challenges in clinic. Especially in the prognosis of treatment, the recurrence rate is often high. In recent years, the role of immune factors in a variety of inflammatory diseases has been gradually revealed, and the expression level of immune factors is closely related to the prognosis of many diseases [2]. At present, the urgent research direction is to explore the correlation between the expression of immune factors and the prognosis of surgical treatment of PCM, and how to predict the effect of surgical treatment by using the expression of immune factors. In PCM, immune factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and interleukin 10 (IL-10) can affect the progress and prognosis of the disease by influencing inflammatory reaction, cell proliferation and death [3]. Study has shown that the expression level of immune factors is closely related to the prognosis of surgical treatment of PCM [4]. Immune factors play an important role in the pathogenesis of PCM and the prognosis of surgical treatment. By understanding the expression patterns of different immune factors, clinicians can better understand the disease mechanism, formulate more accurate treatment plans, and may optimize the treatment results by predicting the prognosis of the disease. Through in-depth study on the role of immune factors in PCM and its correlation with the prognosis of surgical treatment, it will help to develop new treatment strategies, improve the effectiveness of disease management and provide better medical services for patients. Based on this, this study compared and analyzed the correlation and predictive value of TNF-α, IL-6 and IL-10 with the prognosis of surgical treatment of PCM.

2. Data and Methods
2.1 General Data

89 female patients with PCM treated in our hospital from June 2020 to September 2022 were followed up after operation, and were divided into good prognosis group (69 cases) and poor prognosis group (20 cases) according to the evaluation criteria of curative effect. Inclusion criteria: ① female patients diagnosed as PCM by breast ultrasound, galactography, molybdenum target X-ray and biopsy [5]; ② both patients and their families signed an informed commitment letter. Exclusion criteria: ① those who were treated with hormones, immunosuppressants and other related drugs one month before admission; ② patients with malignant tumor diseases.

2.2 Treatment and Follow-up

After ultrasonic examination and location, patients were disinfected and covered with towels. Then 2% lidocaine (China Suicheng Pharmaceutical Co., Ltd., Xinzheng, Henan, China) was used for infiltration anesthesia, and simple tumor resection or segmental mastectomy was performed. During the operation, the wounds were washed with hydrogen peroxide and diluted iodophor, and the drainage was standardized after the operation. After 4 weeks of treatment, the patient came to our hospital for follow-up review.

2.3 Assays for TNF-α, IL-6 and IL-10

The clinical indexes of the two groups were observed, including the stage of onset and the location of lesions. At the time of admission and after 4 weeks of treatment, 5 mL venous blood was taken from the patients, and the supernatant was centrifuged at 3000 r/min for 10 min, then stored in the refrigerator at –20 °C for later use. The immune factors TNF-α (model XY0001H246, Shanghai Enzyme Linked mlbio Biotechnology Co., Ltd., Shanghai, China), IL-6 (model XY001H483, Shanghai Enzyme Linked mlbio Biotechnology Co., Ltd., Shanghai, China) and IL-10 (model XY001H483, Shanghai Enzyme Linked mlbio Biotechnology Co., Ltd., Shanghai, China) were tested by enzyme-linked immunosorbent assay (ELISA). According to the requirements of the kit instructions, the serum samples were diluted and added to the corresponding wells of ELISA microplates, and the corresponding enzyme-labeled antibodies (dilution ratio of 1:100) were added to each well, and incubated in an incubator at 37 °C for 1.5 h. The microplates were washed with washing buffer to remove unbound antibodies, and enzyme substrate solution was added. After waiting for the reaction for 30 min, the color development was observed, and the stop solution was added to stop the reaction and form a stable color development. Finally, the light absorption value (optical density (OD) value) of each hole was measured at the wavelength of 450 nm using an enzyme-labeled instrument (RT-6000, Shenzhen Redu Technology Co., Ltd., Shenzhen, Guangdong, China).

2.4 Prognostic Criteria

Cure: fistula and lump disappeared completely; improvement: the mass is obviously reduced, without pain and fever, and the fistula is close to closure; unhealed: the lump did not disappear and the fistula persisted; total effective = cure + improvement. All patients were evaluated 4 weeks after operation. Patients who were cured and improved were included in the good prognosis group, and the rest were included in the poor prognosis group.

2.5 Observation Indicators

(1) Follow-up for 4 weeks, and compare the levels of immune factors TNF-α, IL-6 and IL-10 before and after treatment. (2) Statistic the prognosis after 4 weeks of treatment, and divide them into poor prognosis group and good prognosis group, and compare the baseline data [age, body mass index (BMI), onset side, clinical stage, nipple status, marital status, menstrual condition and course of disease] and the levels of immune factors TNF-α, IL-6 and IL-10 between the two groups.

2.6 Statistical Analysis

Sample size calculation basis, in which µα = 0.83, µβ = 0.36, and the sample size required for calculation and research is 89 cases. SPSS 26.0 (IBM Corp., Armonk, NY, USA) statistical software was used for analysis. The measurement data were expressed by (x¯ ± s) and compared by independent sample t test. The counting data were expressed in n (%), and the χ2 tests or Fisher’s precision probability tests were used. Pearson correlation analysis was used to analyze the correlation between the expression of immune factors and the prognosis of PCM. Logistic regression was used to analyze the influencing factors of prognosis of PCM after surgical treatment. Draw the receiver operating characteristic (ROC) curve, and analyze the value of immune factors in predicting the prognosis of surgical treatment of PCM. The significance level was set as p < 0.05.

3. Results
3.1 Baseline Clinical Characteristics

Four weeks after the baseline data of the two groups were compared, 20 patients (22.47%) had poor prognosis and 69 patients (77.53%) had good prognosis. The clinical data of the two groups were compared as follows, and there was no significant difference (p > 0.05). See Table 1.

Table 1. Comparison of baseline data between two groups of patients.
Variable Poor prognosis group (n = 20) Good prognosis group (n = 69) t/χ2 p
Age (years) 31.65 ± 6.47 32.16 ± 6.03 0.327 0.743
BMI (kg/m2) 22.45 ± 2.13 22.36 ± 2.57 0.142 0.886
Onset side Unilateral 17 (85.00) 61 (88.41) - 0.705*
Bilateral 3 (15.00) 8 (11.59)
Clinical stages Sinus period 9 (45.00) 32 (46.38) - 0.899*
Abscess stage 5 (25.00) 17 (24.64)
Mass stage 4 (20.00) 15 (21.73)
Overflow period 2 (10.00) 5 (7.25)
Nipple state Normal 5 (25.00) 18 (26.08) 0.358 0.836
Mild depression 11 (55.00) 41 (59.42)
Complete depression 4 (20.00) 10 (14.50)
Marital status Be unmarried 17 (85.00) 57 (82.61) - 1.000*
Married 3 (15.00) 12 (17.39)
Menstrual condition Law 5 (25.00) 17 (24.64) - 1.000*
Indiscipline 15 (75.00) 52 (75.36)
Course of disease (days) 32.24 ± 2.65 33.26 ± 2.54 1.566 0.121
TNF-α (pg/mL) 72.19 ± 7.53 73.24 ± 7.24 0.556 0.572
IL-6 (pg/mL) 348.27 ± 39.36 346.95 ± 37.16 0.138 0.890
IL-10 (ng/mL) 96.44 ± 18.47 95.87 ± 19.26 0.117 0.906

*Fisher’s precision probability test. BMI, body mass index; TNF-α, tumor necrosis factor α; IL-6, interleukin 6; IL-10, interleukin 10.

3.2 Comparison of Immune Factor Levels at Admission and after 4 Weeks of Treatment

After 4 weeks of treatment, the levels of TNF-α and IL-6 in patients were significantly lower than before treatment (p < 0.05), and the level of IL-10 was significantly higher than before treatment (p < 0.05). See Table 2.

Table 2. Comparison of immune factors between patients at admission and after 4 weeks of treatment (n = 89).
Factor On admission After 4 weeks of treatment t p
TNF-α (pg/mL) 73.00 ± 7.28 39.58 ± 5.68 34.145 <0.001
IL-6 (pg/mL) 347.25 ± 37.44 208.35 ± 31.72 26.704 <0.001
IL-10 (ng/mL) 96.00 ± 18.98 136.81 ± 29.14 11.071 <0.001
3.3 Comparison of Immune Factors between Two Groups after 4 Weeks of Treatment

After 4 weeks of treatment, the poor prognosis group had higher levels of TNF-α and IL-6 than the good prognosis group, and lower levels of IL-10 than the good prognosis group (p < 0.05). See Table 3.

Table 3. Comparison of immune factors between two groups after 4 weeks of treatment.
Factor Poor prognosis group (n = 20) Good prognosis group (n = 69) t p
TNF-α (pg/mL) 46.35 ± 5.13 37.62 ± 4.13 7.870 <0.001
IL-6 (pg/mL) 248.34 ± 26.56 196.76 ± 22.33 8.709 <0.001
IL-10 (ng/mL) 121.23 ± 23.18 141.32 ± 29.27 2.820 0.005
3.4 Logistic Regression Analysis of the Prognosis of Surgical Treatment of PCM

Taking the prognosis of surgical treatment of PCM as the dependent variable (good prognosis = 0; poor prognosis = 1). Taking TNF-α, IL-6 and IL-10 as independent variables, logistic regression analysis showed that TNF-α (odds ratio (OR) = 1.551, 95% confidence interval (95% CI): 1.276–1.886) and IL-6 (OR = 1.082, 95% CI: 1.046–1.119) were risk factors for the prognosis of PCM after surgical treatment. See Table 4.

Table 4. Logistic regression analysis of prognosis of surgical treatment for plasma cell mastitis.
Factor β Standard error Wald p OR 95% CI
TNF-α 0.439 0.100 19.414 <0.001 1.551 1.276–1.886
IL-6 0.079 0.017 20.976 <0.001 1.082 1.046–1.119
IL-10 –0.026 0.010 6.852 0.009 0.974 0.955–0.993

OR, odds ratio; 95% CI, 95% confidence interval.

3.5 Correlation Analysis between the Expression of Immune Factors and the Prognosis of Surgical Treatment of PCM

Pearson correlation analysis showed that TNF-α and IL-6 were negatively correlated with the prognosis of surgical treatment of PCM, and IL-10 was positively correlated with the prognosis of surgical treatment of PCM. That is, the lower the indexes of TNF-α and IL-6 and the higher the indexes of IL-10, the better the prognosis of patients with PCM. See Table 5.

Table 5. Correlation analysis between immune factor expression and prognosis of plasma cell mastitis after surgical treatment.
Factor Prognosis of surgical treatment of plasma cell mastitis
Determinant coefficient p
TNF-α –0.645 <0.001
IL-6 –0.682 <0.001
IL-10 0.289 0.006
3.6 Predictive Value of Immune Factor Expression on Prognosis of Surgical Treatment of PCM

The prognosis of surgical treatment of PCM was taken as a state variable (good prognosis = 1; poor prognosis = 0), using TNF-α, IL-6 and IL-10 as independent variables, and drawing ROC curve, as shown in Fig. 1. The results show that the area under the ROC curve (AUC) values of TNF-α, IL-6 and IL-10 are all above 0.600, which shows that the above indexes have good predictive value for the prognosis of surgical treatment of PCM. See Table 6.

Fig. 1.

ROC curve of TNF-α, IL-6, IL-10 and their combination in predicting the prognosis of surgical treatment of plasma cell mastitis. ROC, receiver operating characteristic.

Table 6. Predictive value of immune factor expression on prognosis of plasma cell mastitis after surgical treatment.
Factor AUC p 95% CI Specificity Sensitivity Youden’s index
TNF-α 0.896 <0.001 0.802–0.991 0.928 0.750 0.678
IL-6 0.931 <0.001 0.873–0.989 0.957 0.650 0.607
IL-10 0.709 0.005 0.583–0.836 0.850 0.522 0.372
Combined index 0.945 <0.001 0.881–0.990 0.961 0.649 0.610

AUC, area under the ROC curve; 95% CI, 95% confidence interval.

4. Discussion

PCM, also known as plasma cell mastitis, is a rare chronic inflammatory disease. This disease is usually caused by nipple invagination and difficulty in excreting mammary duct secretions, which may cause abnormal mammary secretion. It causes chemical inflammatory reaction, and with the continuous progress of the disease, it forms a local mass, which causes great trouble to women’s physical and mental health. The disease usually occurs in middle-aged and elderly women and is related to the abnormal function of autoimmune system. Surgical treatment is one of the commonly used methods to treat PCM at present, which mainly includes local excision, mass excision or partial mastectomy. The main purpose of surgery is to remove inflammatory tissue, relieve the pain and discomfort of patients and prevent the spread of lesions [6].

At home and abroad, the evaluation of surgical prognosis mainly focuses on the survival rate, recurrence rate and quality of life of patients. According to study [7], the vast majority of patients with PCM after surgical treatment can obtain good therapeutic effect, with low postoperative recurrence rate and significantly improved quality of life. However, one study has pointed out that [8], a few patients may have recurrence after operation or need further surgical treatment. In addition, with the deepening of the understanding of the disease, some experts and scholars began to explore more conservative or personalized treatment strategies, such as drug treatment and course adjustment [9], in order to achieve better treatment results and lower recurrence rate. In any case, the study on the prognosis of surgical treatment of PCM has always been one of the focuses of medical and scientific research fields. Because the etiology of PCM is unclear, it brings great difficulties to the diagnosis and treatment of the disease. At present, most scholars consider that the disease is related to the immune system dysfunction of patients, so most scholars do a series of clinical study from the perspective of patients’ immune system [10].

Immune factor refers to various molecules and cellular components that play a role in identifying, coping with and destroying foreign substances (such as pathogens, viruses, bacteria, etc.) or abnormal cells in the body (such as cancer cells) in the immune system. Immune factors include cytokines, growth factors and other signal molecules. According to modern medical research, cytokines are mainly divided into two categories: pro-inflammatory factors and anti-inflammatory factors. The normal immune function of the body needs the balance of these two factors, and once they change, the immune response of the body will also be affected [11]. Besides IL-6, TNF-α is also a major pro-inflammatory factor. In contrast, IL-10 is a typical anti-inflammatory factor, which can relieve inflammation. IL-6 is a cytokine with multiple functions, which can promote inflammation and fight infection at the same time. It is produced by a variety of cells such as macrophages, T cells, B cells and fibroblasts. These cells accumulate at the site of infection or inflammation, releasing more inflammatory mediators. Stimulating B cell differentiation and maturation can promote antibody production, enhance T cell activity, and activate acute phase reaction, including causing liver to produce acute phase protein such as C-reactive protein (CRP) [12, 13], which is very important to fight infection. These effects make IL-6 play a central role in immune response, inflammatory response and cell metabolism. Clinically, measuring the level of IL-6 in blood can help doctors judge the active degree of inflammation and the need for treatment. The results of this study show that patients with poor prognosis after surgical treatment of PCM often have higher IL-6 index than patients with good prognosis. Related study shows that the level of IL-6 usually increases significantly during the onset of mastitis, which is closely related to the role of IL-6 in inflammatory response. IL-6 not only plays a role in the acute stage of mastitis, but also participates in the process of tissue repair and regeneration in the late stage of inflammation.

Similarly, the expression level of TNF-α is high in the patients with poor prognosis in this experiment. TNF-α is an important cytokine produced by cells of immune system (such as macrophages and T cells). It also plays a key role in inflammation and immune response. The main functions of TNF-α include promoting the migration of inflammatory cells to the infected site, increasing the permeability of blood vessels, and making it easier for immune cells to reach the infected area. In addition, TNF-α can also affect the coagulation mechanism and promote the activation of coagulation factors, which can prevent the spread of pathogens in some cases, but it may also lead to slow local blood flow or the formation of small thrombus [14]. When tissues are infected with pathogens, the immune system of the body will react quickly. When Kyoho cells and other immune cells recognize pathogens, they will produce and release TNF-α. TNF-α activates downstream signal transduction pathways, such as nuclear factor kappaB (NF-κB) and mitogen-activated protein kinase (MAPK), by binding its specific receptors. These signal pathways can promote the recruitment and activation of inflammatory cells, increase the production of inflammatory cytokines and aggravate local inflammatory reactions. This means that excessive TNF-α will not only lead to aggravated tissue damage, but also lead to pain and dysfunction [15]. In the case of mastitis, the release of TNF-α is a defense mechanism against pathogen invasion, but excess TNF-α can destroy the structure of breast tissue, affect the normal function of breast, and even lead to apoptosis of breast tissue [16].

Different from IL-6 and TNF-α, the results of this study show that IL-10 is expressed in the serum of patients with poor prognosis. The main function of IL-10 is its anti-inflammatory effect [17]. It can inhibit the activation of immune system through various mechanisms, thus reducing inflammation. For example, IL-10 can directly inhibit macrophages and dendritic cells from producing pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6. It has been found that [18] IL-10 mainly restricts inflammatory reaction and prevents tissue damage by down-regulating the expression of inflammatory cytokines and chemokines (IL-6, TNF-α) and inhibiting effector cells (T cells, monocytes), which reduces the amplification of inflammatory signals, thus helping to control the spread of local inflammatory reaction and systemic inflammation. Clinically, the production of IL-10 is usually regarded as a defense mechanism, aiming at limiting the local and systemic inflammatory response caused by bacterial infection [19]. By inhibiting excessive immune response, IL-10 helps to maintain tissue integrity and function and promotes the repair process after infection. However, the high level of IL-10 may also lead to insufficient inflammatory response and affect the ability of the body to remove pathogens. Therefore, the balance of IL-10 is very important for immune response and disease outcome. Study has shown that the change of IL-10 level is closely related to the clinical manifestations, treatment response and recovery process of mastitis [20]. In addition, exogenous administration of IL-10 or enhancement of its signaling pathway may become a potential strategy for the treatment of severe or chronic mastitis, especially in those cases that do not respond well to conventional antibiotic treatment.

Through Pearson analysis and drawing ROC curve, it can be concluded that the above indexes have good predictive value for the prognosis after surgical treatment. Therefore, in patients with poor prognosis after surgical treatment, we can consider monitoring the changes of immune indexes such as IL-6, TNF-α and IL-10, and find and correct immune system disorders as early as possible, which may be helpful to improve the prognosis of patients. At the same time, the therapeutic strategies for immune system disorders are also worthy of further study and discussion. However, there are still some limitations in this study. For example, the results of statistical analysis are not strong enough due to the limitation of sample size, which is easily influenced by accidental factors. Therefore, it is necessary to increase the sample size and conduct multi-center research in subsequent studies. In addition, as a retrospective experiment, the confirmation of causality is limited. Although we can identify the correlation between factors, we can’t rule out the influence of confounding factors, which makes it difficult to draw a clear causal conclusion. Subsequent studies can use randomized controlled trial (RCT) design to confirm the causal relationship.

5. Conclusions

To sum up, the expression of immune factors is closely related to the postoperative prognosis of PCM. Monitoring the changes of immune factors after operation can not only provide a direct indication of patients’ recovery status, but also help predict the recurrence and long-term results of the disease. Therefore, in clinic, the detection and regulation of immune factors may become an important means to improve the prognosis of patients with PCM. Future research needs to further explore the exact mechanism between specific immune factors and the prognosis of surgical treatment in order to provide patients with more personalized and effective treatment programs.

Availability of Data and Materials

The simulation experiment data used to support the findings of this study are available from the corresponding author upon request.

Author Contributions

Conceptualization: SL and XL. Methodology: SL. Data curation: SL. Writing-original draft: SL. Writing-review and editing: XL. Supervision: XL. Both authors contributed to the article and approved the submitted version. Both authors read and approved the final manuscript. Both authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Ethics Approval and Consent to Participate

The study was reviewed and approved by the Ethics Committee of The Affiliated Cangnan Hospital of Wenzhou Medical University, Approval No. 2024078, and informed consent was obtained from all patients. This study was conducted in accordance with the Declaration of Helsinki.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of Interest

The authors declare no conflict of interest.

References

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