Uchino Kazuya, Ito Akihiko, Wakayama Tomohiko, Koma Yu-ichiro, Okada Tomoyo, Ohbayashi Chiho, Iseki Shoichi, Kitamura Yukihiko, Tsubota Noriaki, Okita Yutaka, Okada Morihito
Department of Cardiothoracic Surgery, Kobe University Medical School, Kobe, Hyogo, Japan.
Cancer. 2003 Sep 1;98(5):1002-7. doi: 10.1002/cncr.11599.
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.
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.
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.
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.
最近,TSLC1(肺癌1中的肿瘤抑制因子)基因已被确定为人类非小细胞肺癌中的一种新型肿瘤抑制因子。据作者所知,尚未使用患者数据和手术样本对TSLC1基因表达的临床相关性进行研究。本研究旨在评估TSLC1基因是否可作为肺腺癌患者预后判定的靶点。
本研究共纳入38例经手术治疗确诊为原发性肺腺癌的患者。通过免疫组织化学和蛋白质印迹分析对手术标本进行TSLC1蛋白表达检测。研究TSLC1表达水平与病理特征以及预后之间的相关性。
所有患者均接受了肿瘤的潜在根治性切除。免疫印迹证实了免疫组织化学评估的TSLC1抗原表达。发现TSLC1蛋白的表达与疾病晚期、淋巴结受累、淋巴管浸润和血管侵犯呈负相关。TSLC1抗原高表达(阳性细胞>70% [n = 14例患者])、中表达(阳性细胞20 - 70% [n = 10例患者])和低表达(阳性细胞<20% [n = 14例患者])的患者4年总生存率分别为84%、28%和7%。此外,据报道,TSLC1蛋白阳性细胞百分比高的肿瘤患者的无病生存期明显优于TSLC1蛋白阳性细胞百分比低的肿瘤患者。
切除的肺腺癌病例中TSLC1表达的缺失或降低与预后不良相关,表明TSLC1是控制肿瘤生物学侵袭性的核心效应基因,并且是预测患者预后的重要生物标志物。这些数据可能有助于检测那些复发风险高的患者,他们可能从辅助治疗等额外治疗策略中获益。