Serum macrophage inhibitory cytokine‐1 as a clinical marker for non–small cell lung cancer

Abstract The aim of this study was to investigate the value of serum macrophage inhibitory factor‐1 (MIC‐1) level in patients with non–small cell lung cancer (NSCLC). Serum samples from 296 patients with NSCLC and 240 healthy controls were collected. The levels of serum MIC‐1 were determined by ELISA. The serum MIC‐1 levels in NSCLC patients were higher than that of the controls (P <.001). Univariate and multivariate Cox regression analysis showed that serum MIC‐1 was an independent prognostic indicator of OS and PFS. Serum MIC‐1 is a valuable biomarker for the diagnosis and prognosis of NSCLC.

37-68 years) were recruited. The patient data were collected, including age, gender, smoking, histological type, grade, stage and outcome. Follow-up information is obtained through telephone survey or WeChat. The last follow-up was on 20 February 2019.
Progression-free survival (PFS) was defined as the time interval between the date of diagnosis and the date of recurrence. Overall survival (OS) was defined as the time interval between the date of diagnosis and the date of death.
The study protocol was approved by the Ethics Committee of the Nanjing Chest Hospital. All patients provided written informed consent before enrolment.

| Measurement of serum MIC-1 and CEA levels
Serum samples were taken from each person prior to the start of the treatment. The sensitive internal sandwich ELISA was used to detect the serum MIC-1 levels. The CEA levels were measured by electrochemiluminescence immunoassay on Roche Elecsys 1010 Analyzer (Roche Diagnostics). All the samples were ignored by the technicians running the tests.

| Statistical analysis
Statistical software (SPSS for Windows, version 18) was used for the analysis. The Mann-Whitney U test was used to determine the difference between the two groups. The cut-off value of the serum concentrations of parameters was calculated using a receiver operating characteristic (ROC) curve. Univariate analysis was performed using the Kaplan-Meier method and the log-rank test. Multivariate analysis was conducted to determine an independent impact on survival using the Cox proportional hazard method. P <.05 was considered statistically significant.

| Serum levels of MIC-1 and CEA in NSCLC patients and healthy controls
The serum levels of MIC-1 in NSCLC patients were higher than those of the controls (1582.31 ± 473.01 pg/mL vs 507.71 ± 107.64 pg/mL, P <.001). The serum CEA levels of NSCLC patients were also higher than those of the controls (29.78 ± 7.71 ng/mL vs 3.36 ± 1.25ng/ mL, P <.001).

| Diagnostic value of MIC-1 and CEA in NSCLC patients
The ROC curve was used to calculate the sensitivity of the marker in separating NSCLC patients from healthy controls. As shown in

| Association between MIC-1 levels and clinicopathological characteristics
The relationship between serum MIC-1 levels and clinicopathological characteristics of lung cancer was analysed. MIC-1 levels were correlated with TNM stage (P =.001), tumour differentiation (P =.001) and lymph node metastasis (P =.004).

| Prognostic value of serum MIC-1 levels for NSCLC patients
Univariate analysis showed that serum MIC-1 levels were correlated with OS (P =.005) and PFS (P =.004, Table 1). In multivariate analysis, MIC-1-positive was significantly correlated with shorter PFS and OS (P =.002 and P =.007). The Kaplan-Meier survival curve further confirmed that PFS and OS of NSCLC patients with MIC-1-positive were significantly shorter than those of NSCLC patients with MIC-1-negative ( Figure 2).

| D ISCUSS I ON
Some studies have shown that MIC-1 can be used as a diagnostic marker for some types of tumours. [7][8][9][10][11] However, the value of serum MIC-1 level in the diagnosis and prognosis of NSCLC has not been fully elucidated. In this study, the levels of MIC-1 in NSCLC were higher than those in healthy controls. The diagnostic sensitivity and specificity of MIC-1 were 63.5% and 95.0% in NSCLC patients. The results showed that MIC-1 was valuable in the diagnosis of NSCLC.
In addition, we found that the levels of MIC-1 were significantly correlated with lymph node metastasis, tumour differentiation and Several limitations of our study warrant discussion. First, we performed the study at a single centre with relatively small sample size.
Second, the expression of MIC-1 in serum of lung cancer patients was detected, but the expression of MIC-1 in lung cancer tissues was not detected. Third, the specific mechanism of the relationship between MIC-1 expression and NSCLC was lacking. Further perspective trial should be performed.
In conclusion, our results suggest that serum MIC-1 may be a valuable biomarker for the diagnosis and prognosis of NSCLC.

ACK N OWLED G EM ENTS
The study was supported by the Major Program of Nanjing Medical Science and Technique Development Foundation (ZKX17044).

CO N FLI C T O F I NTE R E S T
The authors declare no conflicts of interest in this work.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data generated or analysed during this study are included in this article.