Naito Kanako, Sangai Takafumi, Yamashita Keishi
Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara 252-0374, Japan.
Department of Breast and Thyroid Surgery, Kitasato University School of Medicine, Sagamihara 252-0374, Japan.
Biomedicines. 2024 Aug 29;12(9):1964. doi: 10.3390/biomedicines12091964.
Breast cancer (BC) is the most common cancer in women, and therapeutic strategies for it are based on the molecular subtypes of luminal BC, HER2 BC, and triple-negative BC (TNBC) because each subtype harbors different unique genetic aberrations. Recently, features of the tumor microenvironment (TME), especially cancer-associated fibroblasts (CAFs), have been demonstrated to play a critical role in BC progression, and we would like to understand the molecular features of BC CAFs for novel therapeutic strategies. In a recent study, 115 CAF-associated genes (CAFGs) were identified in a public database of microdissection and microarray data (GSE35602) from 13 colorectal cancer (CRC) tumors. Using a public database (GSE10797) of 28 BC tumors, a similar analysis was performed. In BC, 59 genes from the 115 CAFGs identified in CRC (CRC CAFGs) were also closely associated with a CAFs marker, (R = 0.6 or beyond), and was of particular interest as one of the BC CAFGs with the highest expression levels and a close association with expression (R = 0.94) in the cancer stroma of BC tumors. In BC stroma, was followed in expression levels by , , , and . Unexpectedly, and were not as highly associated with expression in the cancer stroma of BC tumors and exhibited low expression. These findings suggested that might be the most relevant conventional CAFs marker in BC, and was actually correlated in expression with many CRC CAFGs, such as . Surprisingly, the SE ratio values of the BC CAFGs were much lower (average SE = 3.8) than those of the CRC CAFGs (SE = 10 or beyond). We summarized the current understanding of BC CAFs from the literature. Finally, in triple-negative BC (TNBC) (n = 5), expression uniquely showed a close association with and expression, representing a myofibroblast (myCAFs) marker in the cancer stroma of the BC tumors, suggesting that myCAFs may be molecularly characterized by TNBC in contrast to other BC phenotypes. In summary, CAFs could have unique molecular characteristics in BC, and such TME uniqueness could be therapeutically targeted in BC.
乳腺癌（BC）是女性中最常见的癌症，其治疗策略基于管腔型BC、HER2 BC和三阴性BC（TNBC）的分子亚型，因为每种亚型都有不同的独特基因畸变。最近，肿瘤微环境（TME）的特征，尤其是癌症相关成纤维细胞（CAFs），已被证明在BC进展中起关键作用，我们希望了解BC CAFs的分子特征以制定新的治疗策略。在最近的一项研究中，在来自13例结直肠癌（CRC）肿瘤的显微切割和微阵列数据公共数据库（GSE35602）中鉴定出115个CAF相关基因（CAFGs）。使用来自28例BC肿瘤的公共数据库（GSE10797）进行了类似分析。在BC中，CRC中鉴定出的115个CAFGs中的59个基因（CRC CAFGs）也与CAFs标志物密切相关（R = 0.6或更高），并且作为BC CAFGs中表达水平最高且与BC肿瘤癌基质中的表达密切相关（R = 0.94）的基因之一特别受关注。在BC基质中，表达水平仅次于、、和。出乎意料的是，和与BC肿瘤癌基质中的表达相关性不高且表达水平较低。这些发现表明可能是BC中最相关的传统CAFs标志物，并且实际上在表达上与许多CRC CAFGs相关，如。令人惊讶的是，BC CAFGs的SE比值（平均SE = 3.8）远低于CRC CAFGs的SE比值（SE = 10或更高）。我们从文献中总结了目前对BC CAFs的认识。最后，在三阴性BC（TNBC）（n = 5）中，表达独特地与和表达密切相关，代表BC肿瘤癌基质中的肌成纤维细胞（myCAFs）标志物，这表明与其他BC表型相比，myCAFs可能在分子水平上具有TNBC的特征。总之，CAFs在BC中可能具有独特的分子特征，并且这种TME独特性可作为BC治疗的靶点。
