MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer.
Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gastric cancer tissues from two independent patient cohorts were analyzed. Protein profiles of the discovery cohort (n = 63) were directly obtained from tumor tissue sections by MALDI imaging. A seven-protein signature was associated with an unfavorable overall survival independent of major clinical covariates. The prognostic significance of three individual proteins identified (CRIP1, HNP-1, and S100-A6) was validated immunohistochemically on tissue microarrays of an independent validation cohort (n = 118). Whereas HNP-1 and S100-A6 were found to further subdivide early-stage (Union Internationale Contre le Cancer [UICC]-I) and late-stage (UICC II and III) cancer patients into different prognostic groups, CRIP1, a protein previously unknown in gastric cancer, was confirmed as a novel and independent prognostic factor for all patients in the validation cohort. The protein pattern described here serves as a new independent indicator of patient survival complementing the previously known clinical parameters in terms of prognostic relevance. These results show that this tissue-based proteomic approach may provide clinically relevant information that might be beneficial in improving risk stratification for gastric cancer patients.
Institute of Pathology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Benjamin
B
Balluff
Sandra
S
Rauser
Stephan
S
Meding
Mareike
M
Elsner
Cedrik
C
Schöne
Annette
A
Feuchtinger
Christoph
C
Schuhmacher
Alexander
A
Novotny
Uta
U
Jütting
Giuseppina
G
Maccarrone
Hakan
H
Sarioglu
Marius
M
Ueffing
Herbert
H
Braselmann
Horst
H
Zitzelsberger
Roland M
RM
Schmid
Heinz
H
Höfler
Matthias P
MP
Ebert
Axel
A
Walch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D009418:S100 Proteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D023084:alpha-Defensins / Q000378:metabolism*
D014408:Biomarkers, Tumor; C486181:CRIP1 protein, human; D002352:Carrier Proteins; D060588:LIM Domain Proteins; D009363:Neoplasm Proteins; D009418:S100 Proteins; C110294:S100A1 protein; D023084:alpha-Defensins; C406413:human neutrophil peptide 1