Reduced plasma APOA1 level is associated with gastric tumor growth in MKN45 mouse xenograft model.
There is no suitable diagnostic and prognostic biomarker for gastric cancer. The biggest hurdles in biomarker discovery are (i) the low abundance of cancer cell-specific proteins that limits their detection and (ii) complex inter-patient variations that complicate the discovery process. To circumvent these issues, we conducted proteomics on the plasma of gastric cancer mouse xenograft and attempted to identify proteins released by cancer cells. MKN45 gastric cancer cells were subcutaneously implanted into immune-incompetent nude mice. Plasma samples collected from mice with different tumor sizes (low, mid and high tumor loads) were subjected to iTRAQ and mass spectrometric analyses. Detection of human APOA1 in mouse plasma was verified and its expression level was shown to be lower in mice with large tumors compared to those with small tumors. Studies on a panel of about 14 gastric cancer cell lines supported the notion that APOA1 in mouse plasma was of human gastric cancer cell origin. While the clinical utility of APOA1 remains to be ascertained with a larger scale study, the current work supported the feasibility of using mouse xenograft model for gastric cancer biomarker discovery.
Chong
Poh-Kuan
PK
Cancer Science Institute of Singapore, National University of Singapore, Singapore. csicpk@nus.edu.sg
Lee
Huiyin
H
Zhou
Jianbiao
J
Liu
Shaw-Cheng
SC
Loh
Marie Chiew Shia
MC
So
Jimmy Bok Yan
JB
Lim
Khong Hee
KH
Yeoh
Khay-Guan
KG
Lim
Yoon-Pin
YP
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D040901:Proteomics / Q000379:methods; D016415:Sequence Alignment; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D016632:Apolipoprotein A-I; D014408:Biomarkers, Tumor