Decreased expression of lysophosphatidylcholine (16:0/OH) in high resolution imaging mass spectrometry independently predicts biochemical recurrence after surgical treatment for prostate cancer.
BACKGROUND
Human prostate cancers are highly heterogeneous, indicating a need for various novel biomarkers to predict their prognosis. Lipid metabolism affects numerous cellular processes, including cell growth, proliferation, differentiation, and motility. Direct profiling of lipids in tissue using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) may provide molecular details that supplement tissue morphology.


METHODS
Prostate tissue samples were obtained from 31 patients, with localized prostate cancer who underwent radical prostatectomy. The samples were assessed by HR-MALDI-IMS in positive mode, with the molecules identified by tandem mass spectrometry (MS/MS). The effect of identified molecules on prostate specific antigen recurrence free survival after radical prostatectomy was determined by Cox regression analysis and by the Kaplan-Meier method.


RESULTS
Thirteen molecules were found to be highly expressed in prostate tissue, with five being significantly lower in cancer tissue than in benign epithelium. MS/MS showed that these molecules were [lysophosphatidylcholine (LPC)(16:0/OH)+H](+), [LPC(16:0/OH)+Na](+), [LPC(16:0/OH)+K](+), [LPC(16:0/OH)+matrix+H](+), and [sphingomyelin (SM)(d18:1/16:0)+H](+). Reduced expression of LPC(16:0/OH) in cancer tissue was an independent predictor of biochemical recurrence after radical prostatectomy.


CONCLUSIONS
HR-MALDI-IMS showed that the expression of LPC(16:0/OH) and SM(d18:1/16:0) was lower in prostate cancer than in benign prostate epithelium. These differences in expression of phospholipids may predict prostate cancer aggressiveness, and provide new insights into lipid metabolism in prostate cancer.
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takayuki
T
Goto
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Naoki
N
Terada
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takahiro
T
Inoue
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takashi
T
Kobayashi
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kenji
K
Nakayama
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yoshiyuki
Y
Okada
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takeshi
T
Yoshikawa
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yu
Y
Miyazaki
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Masayuki
M
Uegaki
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Noriaki
N
Utsunomiya
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yuki
Y
Makino
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Shinji
S
Sumiyoshi
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Toshinari
T
Yamasaki
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomomi
T
Kamba
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Osamu
O
Ogawa
D014408:Biomarkers, Tumor; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D053719:Tandem Mass Spectrometry
D014408:Biomarkers, Tumor; D008244:Lysophosphatidylcholines
biomarker; imaging mass spectrometry; lipid; lysophosphatidylcholine; prostate cancer