Lipid MALDI profile classifies non-small cell lung cancers according to the histologic type

Lee, Geon Kook; Lee, Hee Seok; Park, Young Seung; Lee, Jeong Hwa; Lee, Seok Cheol; Lee, Jong Ho; Lee, Soo Jae; Shanta, Selina Rahman; Park, Hye Min; Kim, Hyo Rim; Kim, In Hoo; Kim, Young Hwan; Zo, Jae Ill; Kim, Kwang Pyo; Kim, Hark Kyun

doi:10.1016/j.lungcan.2011.10.016

« Previous Next »Lung Cancer
Volume 76, Issue 2 , Pages 197-203, May 2012

Lipid MALDI profile classifies non-small cell lung cancers according to the histologic type

Geon Kook Lee
- National Cancer Center, Goyang 410-769, Republic of Korea
- These authors equally contributed to this work.
Hee Seok Lee
- National Cancer Center, Goyang 410-769, Republic of Korea
- These authors equally contributed to this work.
Young Seung Park
- Division of Mass Spectrometry Research, Korea Basic Science Institute, Ochang 363-883, Republic of Korea
- These authors equally contributed to this work.
Jeong Hwa Lee
- Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul 143-701, Republic of Korea
Seok Cheol Lee
- National Cancer Center, Goyang 410-769, Republic of Korea
Jong Ho Lee
- Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul 143-701, Republic of Korea
Soo Jae Lee
- Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul 143-701, Republic of Korea
Selina Rahman Shanta
- Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul 143-701, Republic of Korea
Hye Min Park
- National Cancer Center, Goyang 410-769, Republic of Korea
Hyo Rim Kim
- National Cancer Center, Goyang 410-769, Republic of Korea
In Hoo Kim
- National Cancer Center, Goyang 410-769, Republic of Korea
Young Hwan Kim
- Division of Mass Spectrometry Research, Korea Basic Science Institute, Ochang 363-883, Republic of Korea
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea
Jae Ill Zo
- National Cancer Center, Goyang 410-769, Republic of Korea
- Corresponding author at: Center for Lung Cancer, National Cancer Center, 323 Ilsanro, Ilsan, Goyang, Gyeonggi 410-769, Republic of Korea. Tel.: +82 31 920 1655; fax: +82 31 920 1379.
Kwang Pyo Kim
- Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul 143-701, Republic of Korea
- Corresponding author at: Dept. of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, 143-701, Republic of Korea. Tel.: +82 2 458 7682; fax: +82 2 450 3395.
Hark Kyun Kim
- National Cancer Center, Goyang 410-769, Republic of Korea
- Corresponding author at: Department of Cell and Molecular Biology, Research Institute, National Cancer Center, 323 Ilsanro, Ilsan, Goyang, Gyeonggi 410-769, Republic of Korea. Tel.: +82 31 920 2238; fax: +82 31 920 2006.

Received 27 April 2011; received in revised form 27 September 2011; accepted 23 October 2011. published online 18 November 2011.

Abstract

We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may assist with the histopathologic diagnosis of non-small cell lung cancers (NSCLCs). Twenty-one pairs of frozen, resected NSCLCs and adjacent normal tissue samples were initially analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. A lipid profile that could differentiate cancer and adjacent normal samples with a median accuracy of 92.9% was discovered. Several phospholipids including phosphatidylcholines (PC) {34:1} were overexpressed in lung cancer.

Squamous cell carcinomas and adenocarcinomas were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set. MALDI MS image of 11 discriminatory lipids validated their differential expression according to the histologic type in cancer cells of bronchoscopic biopsy samples. PC {32:0} [M+Na]⁺ (m/z 756.68) and ST-OH {42:1} [M−H]⁻ (m/z 906.89) were overexpressed in adenocarcinomas. Thus, lipid profiles accurately distinguish tumor from adjacent normal tissue and classify non-small cell lung cancers according to the histologic type.

Keywords: Histology-directed MALDI, Histologic type, Lipid, Lung cancer, Phosphatidylcholine