Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer.
OBJECTIVE
Colorectal cancer is one of the most common cancers worldwide. We tested the hypothesis that differences in the expression of certain molecular markers of colon cancer may account for different clinical outcomes.


METHODS
Tissue microarray technology was used to assay the expression of 17 biological markers [beta-catenin, CD44v7, c-myc, cyclin D1, estrogen receptor beta, mitogen-activated protein kinase/extracellular signal-regulated kinase, maspin, matrix metalloproteinase-7 (MMP7), p53, Pin1, peroxisome proliferators-activated receptor-gamma, survivin, T cell transcription factor 4 (TCF4), transforming growth factor beta receptor II (TGFbetaR II), TGFbeta, TROP2, and Wnt] by immunohistochemistry in 620 colon cancer patients. The Cox proportional hazards regression model was applied to analyze the lifetime data, including time to death, time to recurrence, and time to liver metastasis.


RESULTS
All the markers were present at significantly higher expression levels in tumor specimens than in normal colonic specimens. Kaplan-Meier analysis showed that high expression of TROP2, MMP7, and survivin were related to decreased survival; TCF4 and TROP2 were related to disease recurrence; and CD44v7, cyclin D1, MMP7, p53, survivin, and TCF4 were related to liver metastasis. However, the results of the multivariate analysis only showed that expression of MMP7, survivin, and TROP2 were significant predictors of lower patient survival, while TROP2 and MMP7 were significantly related to disease recurrence and liver metastasis, respectively.


CONCLUSIONS
We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.
Fang
Y J
YJ
Department of Colorectal Surgery, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
Lu
Z H
ZH
Wang
G Q
GQ
Pan
Z Z
ZZ
Zhou
Z W
ZW
Yun
J P
JP
Zhang
M F
MF
Wan
D S
DS
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis*; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D000077022:Survivin; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; C499380:TACSTD2 protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7