Dell'Anno Irene, Barone Elisa, Mutti Luciano, Rassl Doris M, Marciniak Stefan J, Silvestri Roberto, Landi Stefano, Gemignani Federica
Department of Biology, University of Pisa, Pisa, Toscana, Italy.
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA.
J Transl Med. 2020 Sep 4;18(1):341. doi: 10.1186/s12967-020-02487-6.
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.
We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan-Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients' overall survival (OS).
We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.
In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.
恶性胸膜间皮瘤（MPM）是一种侵袭性的胸膜肿瘤，主要与接触石棉有关。与其他实体瘤一样，恶性细胞表现出高葡萄糖摄取和糖酵解速率，同时乳酸外流增加到间质空间。单羧酸转运蛋白（MCTs）和伴侣蛋白基底膜联蛋白（CD147）负责乳酸进出细胞，这对于维持细胞内pH稳态和糖酵解至关重要。我们旨在研究基底膜联蛋白、MCT1和MCT4在MPM背景下的临床意义，并评估它们的表达与疾病进展的关系。
我们采用免疫组织化学方法检测了135例MPM患者队列中基底膜联蛋白、MCT1和MCT4的表达，并与15例非MPM胸膜标本进行了比较。此外，通过Kaplan-Meier和Cox分析，我们评估了这些标志物表达高于平均值是否与患者的总生存期（OS）相关。
我们在大多数MPM标本中检测到基底膜联蛋白、MCT1和MCT4的阳性染色。特别是，MCT4在恶性组织中始终呈阳性，但在组织芯片中包含的4例正常胸膜标本中未检测到。在另外15例正常胸膜样本系列中得到了证实。此外，MCT4表达与OS降低显著相关。
在本研究中，基底膜联蛋白的组织表达未被证明可作为MPM患者的诊断或预后标志物。MCT1的表达也无信息价值，因为它与基底膜联蛋白的表达紧密相关。然而，MCT4的表达有望作为诊断/治疗和预后生物标志物。
