Abstract 2371: Glycomics analysis as a potential diagnostic test for lung cancer.
Authors: Ruhaak L. Renee , Kim Kyoungmi , Kelly Karen , Rom William N. , Pass Harvey I. , Lebrilla Carlito B. , Gandara David S. , Miyamoto Suzanne 
Published: August 2014

Objective:

Glycomics is an emerging area for understanding carcinogenesis; studies in glycobiology have documented that aberrant glycosylation accompanies malignant transformation. We have used glycomic profiling of serum using nano-liquid chromatography-mass spectrometry and using biostatistics we report glycomics patterns distinguishing between non-small cell lung cancer cases (NSCLC) versus healthy controls.

Methods:

First, we obtained pre-operative sera of non-small lung cancer cases (Stages I-II) and healthy controls from the NYU biorepository. The serum sample set consisted of 50 lung cancer (adenocarcinoma) patients, 50 healthy controls and 28 COPD patients, matched on gender, smoking status, pack/year for smokers, and as best as possible for age. The samples are analyzed by extracting the N-glycans in sera and measuring the relative concentrations using nano-liquid chromatography-mass spectrometry (nano-LC-MS). Bioinformatic analysis was performed to identify glycans that are differentially present in patients with cancer compared to COPD and healthy controls using feature selection and classification algorithms. We further investigated whether a combination of multiple glycans (i.e. multiplex classifier) could improve predictive performance over individual glycans.

Results:

Of 330 glycans detected in the NYU serum set, twenty glycans were significantly differentiating (either over- or under-expressed) between cancer, COPD and controls at a false discovery rate &lt; 0.05. Of these glycan features, 11 were different between cancer samples and control samples, while 14 glycans differed significantly between cancer samples and COPD samples. COPD samples differed significantly from Control samples for only one glycan in concentration, indicating large similarity in the glycosylation pattern between COPD and controls. Based on the glycomic profiles, cancer cases were well separated from both control and COPD samples, while COPD and control samples were not discriminated well from each other. These results indicate that glycan combinations might lead to improvements in the detection of non-small cell lung cancer.

Conclusions:

NSCLC cases were discriminated from controls and COPD using serum glycan profiles. These findings suggest that glycans that are differentially present in patients with NSCLC compared to normal controls or patients with other conditions have the great potential for a diagnostic test for non-small cell lung cancer. While these preliminary results are promising, extensive validation studies are necessary and in process.

Citation Format: L. Renee Ruhaak, Kyoungmi Kim, Karen Kelly, William N. Rom, Harvey I. Pass, Carlito B. Lebrilla, David S. Gandara, Suzanne Miyamoto. Glycomics analysis as a potential diagnostic test for lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2371. doi:10.1158/1538-7445.AM2013-2371