Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer

Ken Konishi, Hirofumi Yamamoto, Koshi Mimori, Ichiro Takemasa, Tsunekazu Mizushima, Masataka Ikeda, Mitsugu Sekimoto, Nariaki Matsuura, Toshifumi Takao, Yuichiro Doki, Masaki Mori

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Abstract

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.

Original languageEnglish
Pages (from-to)2269-2277
Number of pages9
JournalCancer Science
Volume101
Issue number10
DOIs
Publication statusPublished - Oct 2010

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Colorectal Neoplasms
Recurrence
Neoplasm Metastasis
Survival
Immunohistochemistry
Staining and Labeling
Lung
Messenger RNA
Glycolipids
Inositol
Protein C
Disease-Free Survival
Membrane Proteins
Lymph Nodes
Polymerase Chain Reaction
Antibodies
Liver
Genes
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer. / Konishi, Ken; Yamamoto, Hirofumi; Mimori, Koshi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Sekimoto, Mitsugu; Matsuura, Nariaki; Takao, Toshifumi; Doki, Yuichiro; Mori, Masaki.

In: Cancer Science, Vol. 101, No. 10, 10.2010, p. 2269-2277.

Research output: Contribution to journalArticle

Konishi, K, Yamamoto, H, Mimori, K, Takemasa, I, Mizushima, T, Ikeda, M, Sekimoto, M, Matsuura, N, Takao, T, Doki, Y & Mori, M 2010, 'Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer', Cancer Science, vol. 101, no. 10, pp. 2269-2277. https://doi.org/10.1111/j.1349-7006.2010.01674.x
Konishi, Ken ; Yamamoto, Hirofumi ; Mimori, Koshi ; Takemasa, Ichiro ; Mizushima, Tsunekazu ; Ikeda, Masataka ; Sekimoto, Mitsugu ; Matsuura, Nariaki ; Takao, Toshifumi ; Doki, Yuichiro ; Mori, Masaki. / Expression of C4.4A at the invasive front is a novel prognostic marker for disease recurrence of colorectal cancer. In: Cancer Science. 2010 ; Vol. 101, No. 10. pp. 2269-2277.
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