Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression

• Published in: The Journal of surgical research Vol. 185; no. 1; pp. 136 - 142
• Main Authors: Nasu, Toru, MD, Oku, Yoshimasa, MD, Takifuji, Katsunari, MD, Hotta, Tsukasa, MD, Yokoyama, Shozo, MD, Matsuda, Kenji, MD, Tamura, Koichi, MD, Ieda, Junji, MD, Yamamoto, Naoyuki, MD, Takemura, Shigeki, MD, Nakamura, Yasushi, MD, Yamaue, Hiroki, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Aged; CITED1; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - secondary; Colorectal Neoplasms - surgery; Early Diagnosis; Female; Gene Expression Regulation, Neoplastic; Genetic Markers; Humans; Immunohistochemistry; Lymph node metastasis; Lymphatic Metastasis - genetics; Lymphatic Metastasis - pathology; Male; Middle Aged; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Predictive Value of Tests; Prognosis; Real-Time Polymerase Chain Reaction; Risk Factors; RNA, Messenger - metabolism; Surgery; Transcription Factors - genetics; Transcription Factors - metabolism; Lymph node metastasis; CITED1; Colorectal cancer
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.05.041

Abstract Background The identification of molecular markers that are useful for predicting lymph node metastasis is urgently needed to determine treatment strategies for T1 colorectal cancer (CRC). We previously showed that 10 candidate genes are correlated with de-differentiation at the invasion front of CRC using a gene expression analysis. These 10 genes are potential markers that may predict lymph node metastasis by CRC. Materials and methods Samples were obtained from 161 patients with CRC. Quantitative real-time reverse transcription-polymerase chain reaction assays were performed using 66 T3 samples in order to extract genes correlated with lymph node metastasis. Immunohistochemical studies of the extracted genes were performed on 66 T3 and 95 T1 samples. A univariate analysis followed by a multivariate logistic regression model was used to examine independent risk factors for lymph node metastasis. Results The CITED1 messenger RNA expression was found to be an independent risk factor for lymph node metastasis in T3 CRC patients ( P = 0.040). A high CITED1 protein expression, as detected with immunohistochemistry, was also an independent risk factor in T3 CRC patients ( P = 0.035). In T1 colorectal cancer patients, a high CITED1 protein expression was found to be an independent risk factor for lymph node metastasis ( P = 0.010). The positive predictive and negative predictive values in the T1 colorectal cancer patients were 27.5% and 95.5%, respectively. Conclusions The CITED1 expression is correlated with lymph node metastasis in patients with CRC. In T1 colorectal cancer patients, CITED1 has the potential ability to predict the presence of lymph node metastasis.