Differentiation of cancer cell origin and molecular subtype by plasma membrane N-glycan profiling

Serenus Hua, Mary Saunders, Lauren M. Dimapasoc, Seung Hyup Jeong, Bum Jin Kim, Suhee Kim, Minkyung So, Kwang Sik Lee, Jae Han Kim, Kit Lam, Carlito B Lebrilla, Hyun Joo An

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


In clinical settings, biopsies are routinely used to determine cancer type and grade based on tumor cell morphology, as determined via histochemical or immunohistochemical staining. Unfortunately, in a significant number of cases, traditional biopsy results are either inconclusive or do not provide full subtype differentiation, possibly leading to inefficient or ineffective treatment. Glycomic profiling of the cell membrane offers an alternate route toward cancer diagnosis. In this study, isomer-sensitive nano-LC/MS was used to directly obtain detailed profiles of the different N-glycan structures present on cancer cell membranes. Membrane N-glycans were extracted from cells representing various subtypes of breast, lung, cervical, ovarian, and lymphatic cancer. Chip-based porous graphitized carbon nano-LC/MS was used to separate, identify, and quantify the native N-glycans. Structure-sensitive N-glycan profiling identified hundreds of glycan peaks per cell line, including multiple isomers for most compositions. Hierarchical clusterings based on Pearson correlation coefficients were used to quickly compare and separate each cell line according to originating organ and disease subtype. Based simply on the relative abundances of broad glycan classes (e.g., high mannose, complex/hybrid fucosylated, complex/hybrid sialylated, etc.), most cell lines were readily differentiated. More closely related cell lines were differentiated based on several-fold differences in the abundances of individual glycans. Based on characteristic N-glycan profiles, primary cancer origins and molecular subtypes could be distinguished. These results demonstrate that stark differences in cancer cell membrane glycosylation can be exploited to create an MS-based biopsy, with potential applications toward cancer diagnosis and direction of treatment.

Original languageEnglish (US)
Pages (from-to)961-968
Number of pages8
JournalJournal of Proteome Research
Issue number2
StatePublished - Feb 7 2014


  • cancer
  • cell membrane
  • LC/MS
  • mass spectrometry
  • molecular subtype
  • N-glycans

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)


Dive into the research topics of 'Differentiation of cancer cell origin and molecular subtype by plasma membrane N-glycan profiling'. Together they form a unique fingerprint.

Cite this