Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung

• Published in: Cancer Vol. 98; no. 5; pp. 1002 - 1007
• Main Authors: Uchino, Kazuya, Ito, Akihiko, Wakayama, Tomohiko, Koma, Yu‐ichiro, Okada, Tomoyo, Ohbayashi, Chiho, Iseki, Shoichi, Kitamura, Yukihiko, Tsubota, Noriaki, Okita, Yutaka, Okada, Morihito
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2003; Wiley-Liss
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Biological and medical sciences; biomarker; Biomarkers, Tumor; Blotting, Western; Cell Adhesion Molecule-1; Cell Adhesion Molecules; expression; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Immunoglobulins; Immunohistochemistry; lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Medical sciences; Membrane Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Pneumology; Prognosis; Protein Biosynthesis; Proteins - analysis; pulmonary adenocarcinoma; TSLC1; TSLC1 gene; Tumor Suppressor Proteins; Tumors of the respiratory system and mediastinum; Adenocarcinoma; Human; Lung disease; Prognosis; expression; Respiratory disease; Biological marker; Malignant tumor; Gene expression; biomarker; Bronchopulmonary; Bronchus disease; Genetics; TSLC1; Tumor suppressor gene; pulmonary adenocarcinoma
• DOI: 10.1002/cncr.11599
• ISSN: 0008-543X

BACKGROUND Recently, the TSLC1 (tumor suppressor in lung cancer 1) gene has been identified as a novel tumor suppressor in human nonsmall cell lung carcinoma. To the authors' knowledge, the clinical relevance of TSLC1 gene expression has not been studied using patient data and surgical samples. The current study was designed to evaluate whether the TSLC1 gene can serve as a target for the prognostic determination of patients with pulmonary adenocarcinoma. METHODS A total of 38 patients who were surgically treated for proven primary lung adenocarcinoma were enrolled in the current study. Surgical specimens were examined for TSLC1 protein expression immunohistochemically and by Western blot analysis. The correlation between levels of TSLC1 expression and pathologic characteristics, as well as prognosis, was investigated. RESULTS All patients underwent a potentially curative resection of their tumor. TSLC1 antigen expression as evaluated by immunohistochemistry was confirmed by immunoblotting. The expression of TSLC1 protein was found to be inversely correlated with advanced disease stage, lymph node involvement, lymphatic permeation, and vascular invasion. The 4‐year overall survival rates of patients with a tumor demonstrating high (> 70% positive cells [n = 14 patients]), intermediate (20–70% positive cells [n = 10 patients]), and low (< 20% positive cells [n = 14 patients]) expression of the TSLC1 antigen were 84%, 28%, and 7%, respectively. In addition, the disease‐free survival of patients with a tumor that demonstrated a high percentage of TSLC1 protein‐positive cells was reported to be significantly better than that of patients with a tumor that showed a low percentage of TSLC1 protein‐positive cells. CONCLUSIONS The loss or reduction of TSLC1 expression in resected lung adenocarcinoma cases was associated with a poor prognosis, indicating that TSLC1 represents a central effector gene for controlling the biologic aggressiveness of the tumor and that it is an essential biomarker for predicting patient prognosis. These data may help to detect those patients at high risk for recurrence who might benefit from additional therapeutic strategies such as adjuvant therapy. Cancer 2003;98:1002–7. © 2003 American Cancer Society. DOI 10.1002/cncr.11599 The expression of the tumor suppressor gene TSLC1 was examined in surgical specimens from patients with lung adenocarcinoma. A reduced expression of TSLC1 protein was found to correlate with advanced stage and a worse survival, suggesting that TSLC1 might be an important biomarker of the disease that may serve as a predictor of patient prognosis.