Identification of alpha-actinin 4 and 67 kDa laminin receptor as stage-specific markers in esophageal cancer via proteomic approaches.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies in the world with a very poor prognosis. The majority of ESCC patients present with advanced metastatic disease upon diagnosis. Therefore, it is important to understand the molecular mechanism in the tumor invasion process and to find new biomarkers for early diagnosis and prognostic evaluation.


METHODS
Differentially expressed proteins among different stages of primary ESCCs and their matched surrounding normal tissues were compared by proteomics-based technology. The correlations between interesting proteins and clinical features of ESCC were further investigated by using ESCC tissue microarray (TMA) by immunohistochemical staining.


RESULTS
Compared with normal tissues, a total of 18 differentially expressed proteins were identified in ESCC in this study. Among them, expression levels of alpha-actinin 4 (ACTN4) and 67 kDa laminin receptor (67LR) were progressively increased from stage I to III. Clinicopathological correlation using TMA revealed that overexpression of ACTN4 was significantly associated with advanced tumor stage (P = .026) and lymph node metastasis (P = .049), whereas overexpression of 67LR was significantly correlated with advanced tumor stage (P = .019) but not lymph node metastasis.


CONCLUSIONS
These findings suggested that overexpression of ACTN4 and 67 LR is associated with ESCC progression and that these biomarkers may potentially be useful to prognostic evaluation, molecular biological classification, and therapeutic targeting.
Fu
Li
L
Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong, China.
Qin
Yan Ru
YR
Xie
Dan
D
Chow
Hoi Yee
HY
Ngai
Sai Ming
SM
Kwong
Dora L W
DL
Li
Yan
Y
Guan
Xin Yuan
XY
D000185:Actinin / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D040081:Protein Array Analysis; D040901:Proteomics; D017474:Receptors, Laminin / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C111453:ACTN4 protein, human; D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D017474:Receptors, Laminin; D000185:Actinin