Long form collapsin response mediator protein-1 (LCRMP-1) expression is associated with clinical outcome and lymph node metastasis in non-small cell lung cancer patients.
Collapsin response mediator protein (CRMP) family proteins are cytosolic phosphoproteins involved in semaphorin 3A-mediated neuronal cell growth cone collapse and cancer invasion. We identified a novel human isoform of CRMP family proteins named long form CRMP-1 (LCRMP-1), which was different from the known invasion suppressor, CRMP-1, in its molecular weight and the N-terminal exon-1. This study was aimed to elucidate the clinical significance of LCRMP-1 in non-small cell lung cancer (NSCLC) patients. Full-length human LCRMP-1 was cloned from lung adenocarcinoma based on the Expressed Sequence Tags (EST) database. We generated LCRMP-1 specific antibody and subsequent in vitro and in vivo invasion assays showed positive correlations between LCRMP-1 expression and lung cancer cell invasiveness. We further demonstrated that high LCRMP-1 mRNA expressions were associated with poor overall and disease-free survivals (P=0.004 and 0.006, respectively, log-rank test) in 72 NSCLC patients. The results were confirmed in an independent cohort of 54 NSCLC patients by immunohistochemistry (P=0.032, log-rank test). The metastatic lymph nodes showed higher LCRMP-1 expressions as compared with the paired primary lung tumors (P=0.012, McNemar's test). In conclusion, LCRMP-1 was a cancer invasion enhancer that could be a novel prognostic biomarker in NSCLC.
Pan
Szu-Hua
SH
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Chao
Yu-Chih
YC
Chen
Hsuan-Yu
HY
Hung
Pei-Fang
PF
Lin
Pei-Ying
PY
Lin
Chung-Wu
CW
Chang
Yih-Leong
YL
Wu
Chen-Tu
CT
Lee
Yung-Chie
YC
Yang
Shuenn-Chen
SC
Hong
Tse-Ming
TM
Yang
Pan-Chyr
PC
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D015331:Cohort Studies; D018572:Disease-Free Survival; D005091:Exons / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D000098855:Collapsin Response Mediator Protein 1
D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1