High monocarboxylate transporter 4 protein expression in stromal cells predicts adverse survival in gastric cancer.
BACKGROUND
Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC.


METHODS
Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data.


RESULTS
High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value.


CONCLUSIONS
These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, PR China E-mail : y9621227@163.com.
Ping
P
Yan
Yu-Hong
YH
Li
Zhi-Jiao
ZJ
Tang
Xiang
X
Shu
Xia
X
Liu
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases