Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer.
Metastasis-associated gene C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. The aim of this study was to explore the expression and clinical relevance of C4.4A in colorectal cancer. By quantitative RT-PCR, 154 colorectal cancer tissues were examined for C4.4A mRNA. We examined 132 colorectal cancer tissues by immunohistochemistry using a new polyclonal antibody that recognizes the C4.4A protein C-terminus containing the glycosylphosphatidyl-inositol anchor signaling sequence. A significant difference in 5-year overall survival was found between samples with high and low expression of C4.4A mRNA (P = 0.0005). Immunohistochemistry showed strong membranous staining of C4.4A at the invasive front of colorectal cancer tumors and at the frontier of metastatic lesions to lymph node and lung. The membranous staining with enhanced intensity at the invasive front of the primary colorectal cancer (Type A: 34/132, 25.6%) was associated with depth of invasion (P = 0.033) and venous invasion (P = 0.003), and was a significant independent prognostic factor (5-year overall survival in the entire series [n = 132; P = 0.004] and disease-free survival in stage II and III colorectal cancers [n = 82; P = 0.003]). Moreover, Type A C4.4A expression was linked to shorter liver metastasis-free survival rate, lung metastasis-free survival rate, or hematogenous metastasis-free survival (P = 0.0279, P = 0.0061, and P = 0.0006, respectively). Our data indicate that expression of the C4.4A protein at the invasive front acts as a novel prognostic marker in colorectal cancer, possibly through invasion-related mechanisms.
Konishi
Ken
K
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yamamoto
Hirofumi
H
Mimori
Koshi
K
Takemasa
Ichiro
I
Mizushima
Tsunekazu
T
Ikeda
Masataka
M
Sekimoto
Mitsugu
M
Matsuura
Nariaki
N
Takao
Toshifumi
T
Doki
Yuichiro
Y
Mori
Masaki
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000401:mortality* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C472589:LYPD3 protein, human; D012333:RNA, Messenger
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