Acland Mitchell, Arentz Georgia, Mussared Max, Whitehead Fergus, Hoffmann Peter, Klingler-Hoffmann Manuela, Oehler Martin K
Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
School of Mathematical Sciences, The University of Adelaide, Adelaide, SA, Australia.
Front Oncol. 2020 Dec 15;10:523989. doi: 10.3389/fonc.2020.523989. eCollection 2020.
Serous endometrial cancer (SEC) and high grade serous ovarian cancer (HGSOC) are aggressive gynecological malignancies with high rates of metastasis and poor prognosis. Endometrial intraepithelial carcinoma (EIC), the precursor for SEC, and serous tubal intraepithelial carcinoma (STIC), believed to be the precursor lesion for HGSOC, can also be associated with intraabdominal spread. To provide insight into the etiology of these precancerous lesions and to explore the potential molecular mechanisms underlying their metastatic behavior, we performed a proteomic mass spectrometry analysis in a patient with synchronous EIC and STIC. Through histological and molecular identification of precancerous lesions followed by laser capture microdissection, we were able to identify over 450 proteins within the precancerous lesions and adjacent healthy tissue. The proteomic analysis of STIC and EIC showed remarkable overlap in the proteomic patterns, reflecting early neoplastic changes in proliferation, loss of polarity and attachment. Our proteomic analysis showed that both EIC and STIC, despite being regarded as premalignant lesions, have metastatic potential, which correlates with the common presentation of invasive serous gynecological malignancies at advanced stage.
浆液性子宫内膜癌（SEC）和高级别浆液性卵巢癌（HGSOC）是侵袭性妇科恶性肿瘤，转移率高且预后不良。子宫内膜上皮内癌（EIC）是SEC的前驱病变，而浆液性输卵管上皮内癌（STIC）被认为是HGSOC的前驱病变，它们也可能与腹腔内播散有关。为了深入了解这些癌前病变的病因，并探索其转移行为背后的潜在分子机制，我们对一名同时患有EIC和STIC的患者进行了蛋白质组质谱分析。通过对癌前病变进行组织学和分子鉴定，随后进行激光捕获显微切割，我们能够在癌前病变及相邻健康组织中鉴定出450多种蛋白质。对STIC和EIC的蛋白质组分析显示，蛋白质组模式有显著重叠，反映了增殖、极性丧失和黏附方面的早期肿瘤变化。我们的蛋白质组分析表明，尽管EIC和STIC被视为癌前病变，但它们都具有转移潜能，这与晚期侵袭性浆液性妇科恶性肿瘤的常见表现相关。
