应用MALDI-TOF-MS检测肺鳞癌患者血清多肽并分析其与化疗疗效相关性

BACKGROUND AND OBJECTIVE: Treatment options for patients with squamous cell carcinoma of the lung (SCC) are limited in chemotherapy. However, not all patients could benefit form standard platinum regimen. Considering the dismal prognosis of patients with advanced SCC, a greater focus on selecting sensitive chemotherapy regimens remains of upmost importance to improve outcomes in this disease. In this study, we used matrix-assisted laser desorption/ionization timeof-flight mass spectrometry to detect pre-chemotherapy serum peptides in advanced lung squamous cell carcinoma patients accepting paclitaxel combined with platinum chemotherapy and to analyze the correlation between serum peptides and chemotherapy efficacy. METHODS: Patients with advanced lung squamous cell carcinoma received paclitaxel combining with platinum chemotherapy and evaluated the efficacy every two cycles. Evaluation of complete response (CR) or partial response (PR) patients defined as sensitive group, progressive disease (PD) patients defined as resistant group. Serum samples were collected from patients with lung squamous cell carcinoma. Eighty-one patients were randomly divided into training group (sensitive group Ⅰ and resistant group Ⅰ) and validation group (sensitive group Ⅱ and resistant group Ⅱ) according to the ratio of 3:1. Serum samples were pretreated and Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was used to detect serum peptide fingerprints. ClinProTools software was used to analyze the differences between the sensitive group Ⅰ and the resistant group Ⅰ. Three kinds of biological algorithms (SNN, GA, QC) built in CPT software were used to establish the curative effect prediction model respectively and the optimal algorithm was selected. The validation group was used for blind verification. RESULTS: Thirty sensitive patients and 31 resistant patients were enrolled in the training group. Ten sensitive patients and 10 resistant patients were included in the validation group. The training group had 96 differentially expressed peptides in the sensitive and resistant patients, with 16 statistically significant peptides (P < 0.001). The predictive model was established by 5 polypeptides (1, 897.75 Da, 2, 023.93 Da, 3, 683.36 Da, 4, 269.56 Da, 5, 341.29 Da). The recognition rate of this model was 89.18% and the cross validation rate was 95.11%. The accuracy of the model was 85%, the sensitivity was 90.0% and the specificity was 80.0%. The median PFS in the sensitive group was better than patients in the resistant group (7.2 months 95%CI: 4.4-14.5 vs 1.8 months 95%CI: 0.7-3.5). The results showed that the differential peptides 4, 232.04 Da and 4, 269.56 Da were correlated with PFS in patients with lung squamous cell carcinoma (P < 0.001). CONCLUSION: MALDI-TOFMS was used to detect the difference of serum peptides between sensitive and resistant groups. The preliminary curative effect prediction model was used to predict the efficacy of paclitaxel combined with platinum regimen. However, this model need further investigations to verify the accuracy and the sensitivity.