西班牙裔/拉丁裔人群早发性结直肠癌中WNT和转化生长因子-β信号通路的改变

WNT and TGF-Beta Pathway Alterations in Early-Onset Colorectal Cancer Among Hispanic/Latino Populations.

作者信息

Monge Cecilia, Waldrup Brigette, Carranza Francisco G, Velazquez-Villarreal Enrique

机构信息

Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Department of Integrative Translational Sciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.

出版信息

Cancers (Basel). 2024 Nov 21;16(23):3903. doi: 10.3390/cancers16233903.

DOI:10.3390/cancers16233903

PMID:39682092

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11639970/

Abstract

BACKGROUND/OBJECTIVES: One of the fastest-growing minority groups in the U.S. is the Hispanic/Latino population. Recent studies have shown how this population is being disproportionately affected by early-onset colorectal cancer (CRC). Compared to corresponding non-Hispanic White (NHW) patients, Hispanic/Latino patients have both higher incidence of disease and rates of mortality. Two well-established drivers of early-onset CRC in the general population are alterations in the WNT and TGF-Beta signaling pathways; however, the specific roles of these pathways in Hispanics/Latinos are poorly understood.

METHODS

Here, we assessed CRC mutations in the WNT and TGF-Beta pathways by conducting a bioinformatics analysis using cBioPortal. Cases of CRC were stratified both by age and ethnicity: (1) early-onset was defined as <50 years vs. late-onset as ≥50 years; (2) we compared early-onset in Hispanics/Latinos to early-onset in NHWs.

RESULTS

No significant differences were evident when we compared early-onset and late-onset CRC cases within the Hispanic/Latino cohort. These results are consistent with findings from large cohorts that do not specify ethnicity. However, we found significant differences when we compared early-onset CRC in Hispanic/Latino patients to early-onset CRC in NHW patients: specifically, alterations in the gene bone morphogenetic protein-7 (BMP7) were more frequent in early-onset CRC for the Hispanic/Latino patients. In addition to these findings, we observed that both NHW patients and Hispanic/Latino patients with early-onset disease had better clinical outcomes when there was evidence of WNT pathway alterations. Conversely, the absence of TGF-Beta pathway alterations was uniquely associated with improved outcomes exclusively in early-onset Hispanic/Latino patients.

CONCLUSIONS

In toto, these findings underscore how the WNT and TGF-Beta pathways may act differently in different ethnic groups with early-onset CRC. These findings may set a stage for developing new therapies tailored for reducing cancer health disparities.

摘要

背景/目的：美国增长最快的少数族裔群体之一是西班牙裔/拉丁裔人口。最近的研究表明，该人群正受到早发性结直肠癌（CRC）的不成比例影响。与相应的非西班牙裔白人（NHW）患者相比，西班牙裔/拉丁裔患者的疾病发病率和死亡率都更高。WNT和TGF-β信号通路的改变是普通人群早发性CRC的两个公认驱动因素；然而，这些通路在西班牙裔/拉丁裔中的具体作用尚不清楚。

方法

在此，我们通过使用cBioPortal进行生物信息学分析，评估了WNT和TGF-β通路中的CRC突变。CRC病例按年龄和种族分层：（1）早发性定义为<50岁，晚发性定义为≥50岁；（2）我们将西班牙裔/拉丁裔的早发性与NHW的早发性进行了比较。

结果

当我们比较西班牙裔/拉丁裔队列中的早发性和晚发性CRC病例时，没有明显差异。这些结果与未指定种族的大型队列研究结果一致。然而，当我们将西班牙裔/拉丁裔患者的早发性CRC与NHW患者的早发性CRC进行比较时，发现了显著差异：具体而言，骨形态发生蛋白7（BMP7）基因的改变在西班牙裔/拉丁裔患者的早发性CRC中更为频繁。除了这些发现，我们还观察到，当有WNT通路改变的证据时，NHW患者和早发性疾病的西班牙裔/拉丁裔患者都有更好的临床结果。相反，TGF-β通路改变的缺失仅与早发性西班牙裔/拉丁裔患者的预后改善独特相关。