Rana Priyanka Shailendra, Wang Wei, Alkrekshi Akram, Markovic Vesna, Khiyami Amer, Chan Ricky, Perzynski Adam, Joseph Natalie, Sossey-Alaoui Khalid
Department of Medicine, MetroHealth Medical Center, Cleveland, OH 44109, USA.
Case Western Reserve University School of Medicine, Case Western Reserve University, Cleveland, OH 44016, USA.
Cancers (Basel). 2021 Dec 14;13(24):6262. doi: 10.3390/cancers13246262.
Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments.
三阴性乳腺癌（TNBC）是所有乳腺癌（BC）亚型中最具侵袭性的。虽然TNBC肿瘤在所有BC亚型中所占比例不到20%，但它们导致了大多数与BC相关的死亡。更值得注意的是，在考虑所有种族/族裔群体的TNBC发病率时，TNBC在所有BC中所占比例不到20%。然而，在非西班牙裔黑人女性中，TNBC的发病率超过40%，这可能是该人群中与BC相关的死亡率较高的一个促成因素。即使在考虑了社会经济地位、医疗保健可及性和生活方式因素的差异之后，这些差异仍然很明显。越来越多的证据表明，肿瘤内在的生物学机制导致了TNBC疾病负担的差异。在这里，我们表明，多功能基因YB1在非裔美国（AA）和高加索裔美国（CA）女性的TNBC差异中起主要作用。我们在三个独立的TNBC肿瘤队列中表明，与CA相比，YB1在AA TNBC肿瘤中显著高表达，并且YB1水平的升高与AA TNBC患者的不良生存相关。我们在TNBC的体外和动物模型中结合了YB1的基因操作和化疗治疗，以表明YB1的致癌活性在AA来源的TNBC细胞系中通过激活癌症干细胞表型和对化疗治疗的抗性，增加其致瘤和侵袭行为而得到更大增强。
