Qu Shuoying, Timmermans A Mieke, Heemskerk-Gerritsen Bernadette A M, Trapman-Jansen Anita M A C, Broeren-Foekens Renée, Prager-van der Smissen Wendy J C, El Hassnaoui Hoesna, van Tienhoven Tim, Bes-Stobbe Claudia K, Westenend Pieter J, van Deurzen Carolien H M, Martens John W M, Hooning Maartje J, Hollestelle Antoinette
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Pathan BV, Kleiweg 500, 3045 PM Rotterdam, The Netherlands.
Cancers (Basel). 2023 Dec 20;16(1):28. doi: 10.3390/cancers16010028.
The ferritin-heavy chain (FTH1) is the catalytic subunit of the ferroxidase ferritin, which prevents oxidative DNA damage via intracellular iron storage. FTH1 was shown to be a prognostic marker for triple-negative breast cancer (BC) patients and associated with an enrichment of CD8+ effector T cells. However, whether the expression and localization of FTH1 are also associated with clinical outcome in other BC subtypes is unknown. Here, we investigated the association of FTH1 with time to survival in BCs from 222 mutation carriers by immunohistochemistry on tissue microarrays. In addition, for 51 of these patients, the association between FTH1 and specific subsets of T cells was evaluated on whole slides using automatic scoring algorithms. We revealed that nuclear FTH1 (nFTH1) expression, in multivariable analyses, was associated with a shorter disease-free (HR = 2.71, 95% CI = 1.49-4.92, = 0.001) and metastasis-free survival (HR = 3.54, 95% CI = 1.45-8.66, = 0.006) in patients carrying a mutation. However, we found no relation between cytoplasmic FTH1 expression and survival of mutation carriers. Moreover, we did not detect an association between FTH1 expression and the amount of CD45+ ( = 0.13), CD8+ ( = 0.18), CD4+ ( = 0.20) or FOXP3+ cells ( = 0.17). Consequently, the mechanism underlying the worse recurrence-free survival of nFTH1 expression in mutation carriers needs further investigation.
铁蛋白重链（FTH1）是铁氧化酶铁蛋白的催化亚基，可通过细胞内铁储存防止氧化性DNA损伤。FTH1被证明是三阴性乳腺癌（BC）患者的预后标志物，并与CD8 +效应T细胞的富集有关。然而，FTH1的表达和定位是否也与其他BC亚型的临床结果相关尚不清楚。在这里，我们通过组织微阵列上的免疫组织化学研究了222名突变携带者的BC中FTH1与生存时间的关系。此外，对于其中51名患者，使用自动评分算法在全玻片上评估了FTH1与T细胞特定亚群之间的关联。我们发现，在多变量分析中，核FTH1（nFTH1）表达与携带突变的患者较短的无病生存期（HR = 2.71，95％CI = 1.49-4.92，P = 0.001）和无转移生存期（HR = 3.54，95％CI = 1.45-8.66，P = 0.006）相关。然而，我们发现细胞质FTH1表达与突变携带者的生存之间没有关系。此外，我们未检测到FTH1表达与CD45 +（P = 0.13）、CD8 +（P = 0.18）、CD4 +（P = 0.20）或FOXP3 +细胞数量（P = 0.17）之间的关联。因此，突变携带者中nFTH1表达导致无复发生存期较差的潜在机制需要进一步研究。
