Department of Respiratory Medicine, School of Medicine, Kitasato University, Sagamihara, Japan.
Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.
Thorac Cancer. 2019 Nov;10(11):2142-2151. doi: 10.1111/1759-7714.13200. Epub 2019 Oct 3.
Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis.
IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival.
High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation.
Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.
线粒体功能障碍与许多人类疾病和癌症进展有关。内膜线粒体蛋白（IMMT）在维持线粒体结构和功能方面发挥着重要作用。本研究旨在检测肺腺癌中的 IMMT 表达，并评估其与临床病理参数和患者预后的相关性。
对 176 例连续肺腺癌切除组织进行 IMMT 表达的免疫组织化学研究，并评估其与临床病理参数的相关性。采用 Kaplan-Meier 生存分析和 Cox 比例风险模型估计 IMMT 表达对生存的影响。
在 176 例肺腺癌中，有 84 例（47.7%）检测到高 IMMT 表达。水平与晚期疾病分期（Ⅱ期和Ⅲ期；P = 0.024）、肿瘤较大（>3 cm；P = 0.002）、肿瘤内血管侵犯（P<0.001）和较差的肺腺癌患者预后（P = 0.002）显著相关。基于 176 例腺癌患者，多变量分析显示 IMMT 表达是较差生存的独立预测因子（HR，1.99；95%置信区间[CI]，1.06-3.74；P = 0.031）。此外，用 IMMT siRNA 处理源自肺腺癌的 A549 细胞，导致增殖明显下降。
我们首次证明高 IMMT 表达与一些临床病理参数有关，其表达是肺腺癌患者较差生存的独立预后预测因子；需要进一步研究以阐明 IMMT 在肺腺癌中的生物学功能。然而，结果表明该蛋白可能是一种新的预后指标和治疗靶点。
