Saed Ghassan M, Sharma Harvey, Dabaja Jenna, Nawaz Asad, Alvero Ayesha, Morris Robert T, Basha Asma, Werner Lucas, Parris Toshima Z, Helou Khalil
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Gynecologic Oncology, Karmanos Cancer Institute, 48201, Detroit, MI, USA; Department of Obstetrics and Gynecology, University of Jordan School of Medicine, 226 Queen Rania Al Abdulla St, Amman 11942, Jordan.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Transl Oncol. 2025 Aug 12;61:102495. doi: 10.1016/j.tranon.2025.102495.
Hornerin (HRNR) is part of the S100-fused protein family and has been linked to poorer prognosis in various cancers, though the mechanisms remain unclear. This study aimed to explore the role of HRNR in ovarian cancer.
We conducted proteomic analysis (n = 252) and RNA sequencing (n = 96) on primary ovarian carcinomas to evaluate HRNR expression across different histotypes, survival outcomes, and to identify genetic variants in the HRNR gene. We also assessed HRNR levels in both chemosensitive and chemoresistant ovarian cancer cell lines, as well as in serum samples at different disease stages.
Our findings revealed that HRNR levels were significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, with elevated expression associated with shorter survival. Additionally, HRNR levels increased in sera from late-stage patients compared to those in early stages. We identified several potentially harmful genetic variants in exon 3 of HRNR in patients with high-grade serous carcinoma, including a translocation of a 900 bp fragment from exon 3 to a region between exons 1 and 2. Chemoresistant ovarian cancer cells exhibited higher HRNR levels than chemosensitive cells. Silencing HRNR using siRNA markedly enhanced the cytotoxic effects on all tested ovarian cancer cells.
HRNR plays a significant role in ovarian cancer with potential to serve as a prognostic marker. Additionally, targeting HRNR expression may offer therapeutic benefits, particularly for patients with chemoresistance or specific HRNR genetic variants, highlighting the need for further investigation in the management of ovarian cancer.
Hornerin (HRNR) is linked to poor prognosis in various cancers, but its role in ovarian cancer has been underexplored. Our study shows that HRNR expression is significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, correlating with shorter survival. Elevated HRNR levels in late-stage patients suggest its potential as a prognostic marker. We also identified harmful genetic variants in HRNR, including a novel translocation, which may affect disease progression. Targeting HRNR could enhance chemotherapy effectiveness, particularly for patients with HRNR genetic variants, positioning it as a promising biomarker and therapeutic target in ovarian cancer.
霍纳林（HRNR）是S100融合蛋白家族的一部分，尽管其机制尚不清楚，但已被证明与多种癌症的预后较差有关。本研究旨在探讨HRNR在卵巢癌中的作用。
我们对原发性卵巢癌进行了蛋白质组分析（n = 252）和RNA测序（n = 96），以评估HRNR在不同组织学类型中的表达、生存结果，并鉴定HRNR基因中的遗传变异。我们还评估了化疗敏感和化疗耐药的卵巢癌细胞系以及不同疾病阶段血清样本中的HRNR水平。
我们的研究结果显示，与高级别浆液性癌相比，透明细胞和黏液性卵巢癌中的HRNR水平显著更高，其表达升高与生存期缩短相关。此外，与早期患者相比，晚期患者血清中的HRNR水平升高。我们在高级别浆液性癌患者的HRNR外显子3中鉴定出了几种潜在有害的遗传变异，包括一个900 bp片段从外显子3易位到外显子1和2之间的区域。化疗耐药的卵巢癌细胞比化疗敏感的细胞表现出更高的HRNR水平。使用小干扰RNA（siRNA）沉默HRNR可显著增强对所有测试卵巢癌细胞的细胞毒性作用。
HRNR在卵巢癌中起重要作用，有可能作为一种预后标志物。此外，靶向HRNR表达可能带来治疗益处，特别是对于化疗耐药或具有特定HRNR遗传变异的患者，这突出了在卵巢癌治疗中进一步研究的必要性。
霍纳林（HRNR）与多种癌症的预后不良有关，但其在卵巢癌中的作用尚未得到充分研究。我们的研究表明，与高级别浆液性癌相比，透明细胞和黏液性卵巢癌中的HRNR表达显著更高，与生存期缩短相关。晚期患者中HRNR水平升高表明其作为预后标志物的潜力。我们还在HRNR中鉴定出有害的遗传变异，包括一种新的易位，这可能影响疾病进展。靶向HRNR可提高化疗效果，特别是对于具有HRNR遗传变异的患者，使其成为卵巢癌中有前景的生物标志物和治疗靶点。
