Correlation between small-cell lung cancer serum protein/peptides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemotherapy efficacy

Abstract

Background: Currently, no effective measures are available to predict the curative efficacy of small-cell lung cancer (SCLC) chemotherapy. We expect to develop a method for effectively predicting the SCLC chemotherapy efficacy and prognosis in clinical practice in order to offer more pertinent therapeutic protocols for individual patients.

Methods: We adopted matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinPro Tools system to detect serum samples from 154 SCLC patients with different curative efficacy of standard chemotherapy and analyze the different peptides/proteins of SCLC patients to discover predictive tumor markers related to chemotherapy efficacy. Ten peptide/protein peaks were significantly different in the two groups.

Results: A genetic algorithm model consisting of four peptides/proteins was developed from the training group to separate patients with different chemotherapy efficacies. Among them, three peptides/proteins (m/z 3323.35, 6649.03 and 6451.08) showed high expression in the disease progression group, whereas the peptide/protein at m/z 4283.18 was highly expressed in the disease response group. The classifier exhibited an accuracy of 91.4% (53/58) in the validation group. The survival analysis showed that the median progression-free survival (PFS) of 30 SCLC patients in disease response group was 9.0 months; in 28 cases in disease progression group, the median PFS was 3.0 months, a statistically significant difference (χ² = 46.98, P < 0.001). The median overall survival (OS) of the two groups was 13.0 months and 7.0 months, a statistically significant difference (χ² = 40.64, P < 0.001).

Conclusions: These peptides/proteins may be used as potential biological markers for prediction of the curative efficacy and prognosis for SCLC patients treated with standard regimen chemotherapy.

Keywords: Chemotherapy; Matrix assisted laser desorption ionization-time of flight-mass spectrometry; Prediction of efficacy; Proteomics; Small-cell lung cancer.

Fig. 1

The average spectra of the training set displayed in ClinPro tools. (A) Average spectra for disease response group I in the training group. (B) Average spectra for disease progression group I in the training group

Fig. 2

ClinPro Tools image of the average intensity, in arbitrary units, of four peptides that represent the classifier in disease response group I and disease progression group I. (Red curve: Disease response group I; green curve: Disease progression group I)

Fig. 3

Survival analysis of 58 patients in the validation group. (A) 29 patients were labeled as “Disease response group II” had obviously inferior PFS (P < 0.001) when compared to 29 patients were labeled as “Disease progression group II”. (B) 29 patients were labeled as “Disease response group II” had obviously inferior OS (P < 0.001) when compared to 29 patients were labeled as “Disease progression group II”