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四跨膜蛋白CD63和CD81作为乳腺癌潜在的预后生物标志物。

Tetraspanins CD63 and CD81 as potential prognostic biomarkers in breast cancer.

作者信息

Iwabuchi Erina, Miki Yasuhiro, Xu Junyao, Kanai Ayako, Ishida Takanori, Suzuki Takashi

机构信息

Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Pathology and Anatomical Sciences, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.

出版信息

Breast Cancer. 2025 Mar;32(2):393-403. doi: 10.1007/s12282-025-01666-x. Epub 2025 Jan 14.

Abstract

Exosome markers, CD63 and CD81, belong to the tetraspanin family and are expressed in solid tumors. It has been reported that these tetraspanin family members are prognostic factors in some cancers. However, the expression of CD63 and CD81 in pathological breast cancer specimens has not been reported. It has been reported that CD63 promotes the proliferation of breast cancer cells in vitro through yes-associated protein (YAP). Therefore, in this study, the expression of tetraspanin family members, particularly CD63, CD81, and YAP were investigated in breast cancer tissue, by immunohistochemistry, to clarify the relationship between clinicopathological factors and prognosis. The number of CD63 and YAP double-positive breast cancer cells was significantly higher in patients with pathological T factor (pT) status (p = 0.030) and tended to be higher in patients with pathological N factor (pN) status (p = 0.054). Furthermore, the number of CD81 and YAP double-positive breast cancer cells was significantly higher in patients with histological grade (p = 0.015), pT status (p = 0.001), and Ki67 expression (p = 0.049), and tended to be higher in patients with pN status (p = 0.062) and TNM stage (p = 0.052). In addition, CD63 and YAP double-positive breast cancers and CD81 and YAP double-positive breast cancers were associated with shorter disease-free and breast cancer-specific survival, respectively. In conclusion, CD63 and YAP, and CD81 and YAP may serve as potential prognostic biomarkers in patients with breast cancer.

摘要

外泌体标志物CD63和CD81属于四跨膜蛋白家族,在实体瘤中表达。据报道,这些四跨膜蛋白家族成员在某些癌症中是预后因素。然而,CD63和CD81在病理性乳腺癌标本中的表达尚未见报道。据报道,CD63在体外通过Yes相关蛋白(YAP)促进乳腺癌细胞的增殖。因此,在本研究中,通过免疫组织化学研究了四跨膜蛋白家族成员,特别是CD63、CD81和YAP在乳腺癌组织中的表达,以阐明临床病理因素与预后之间的关系。CD63和YAP双阳性乳腺癌细胞的数量在病理T因子(pT)状态的患者中显著更高(p = 0.030),在病理N因子(pN)状态的患者中趋于更高(p = 0.054)。此外,CD81和YAP双阳性乳腺癌细胞的数量在组织学分级(p = 0.015)、pT状态(p = 0.001)和Ki67表达(p = 0.049)的患者中显著更高,在pN状态(p = 0.062)和TNM分期(p = 0.052)的患者中趋于更高。此外,CD63和YAP双阳性乳腺癌以及CD81和YAP双阳性乳腺癌分别与无病生存期和乳腺癌特异性生存期缩短相关。总之,CD63与YAP以及CD81与YAP可能作为乳腺癌患者潜在的预后生物标志物。

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