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基因组不稳定性评分、肿瘤突变负荷与 TIL(肿瘤浸润淋巴细胞)作为子宫浆液性癌生物标志物的关联

英文原题:Association of Genomic Instability Score, Tumor Mutational Burden, and Tumor-Infiltrating Lymphocytes as Biomarkers in Uterine Serous Carcinoma.

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Association of Genomic Instability Score, Tumor Mutational Burden, and Tumor-Infiltrating Lymphocytes as Biomarkers in Uterine Serous Carcinoma.

PubMed 2023/01/15(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

子宫浆液性癌约占子宫癌的10%,却造成该疾病近40%的死亡。更充分的分子特征分析有助于指导靶向治疗并改善结局。本研究评估了子宫浆液性癌(USC)患者的基因组不稳定评分(GIS)、肿瘤突变负荷(TMB)和TIL(肿瘤浸润淋巴细胞)。

回顾性队列研究纳入接受分期手术后的USC患者。研究者利用存档标本测定GIS和TMB,并通过免疫组织化学评估肿瘤中CD3、CD4、CD8、FOXP3和CD68的表达。采用t检验评估TIL与GIS之间的关联。

共评估53名USC患者。GIS中位数为31(范围:0–52);较高GIS与无进展生存期(PFS)或总生存期(OS)无关。TMB中位数为1.35 mt/Mb;TMB > 1.35 mt/Mb的患者PFS和OS均较好(p分别为0.005和0.002)。CD3⁺和CD4⁺免疫细胞增多的肿瘤,其平均GIS较高(p分别为0.013和0.002)。

TMB > 1.35 mt/Mb与USC患者生存改善相关,而GIS无此关联。较低的TMB阈值可能对免疫原性较低的肿瘤(如USC)具有预后价值。在这一规模有限的队列中,研究观察到TIL群体增加与较高GIS相关。

展开英文摘要原文

Background: Uterine serous carcinomas represent 10% of uterine carcinomas but account for nearly 40% of deaths from the disease. Improved molecular characterization of these tumors is instrumental in guiding targeted treatment and improving outcomes.

This study assessed the genomic instability score (GIS), tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs) in patients with USC. Methods: A retrospective cohort study evaluated patients with USC following staging surgery. The GIS and TMB were determined from archived specimens.

We evaluated the tumoral expression of CD3, CD4, CD8, FOXP3, and CD68 using immunohistochemistry. T-tests were used to assess associations of TILs with the GIS. Results: We evaluated 53 patients with USC. The median GIS was 31 (range: 0 52) and a higher GIS was not associated with progression-free (PFS) or overall survival (OS). The median TMB was 1. 35 mt/Mb; patients with TMB > 1. 35 mt/Mb had improved PFS and OS (p = 0.

005; p = 0. 002, respectively). Tumors with increased CD3+ and CD4+ immune cells had a higher mean GIS (p = 0. 013, p = 0. 002). Conclusions: TMB > 1. 35 mt/Mb was associated with improved survival in USC patients, whereas the GIS was not. Lower TMB thresholds may provide prognostic value for less immunogenic tumors such as USC. In this limited cohort, we observed that increased TIL populations were correlated with a higher GIS.

论文信息

作者
Bloom EA、Peters PN、Whitaker R、Russell S、Albright B、Cummings S、Timms KM、Slavin T
第一作者单位
Duke University School of Medicine, Duke University, Durham, NC 27710, USA.United States
通讯作者单位
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University School of Medicine, Durham, NC 27710, USA.United States
期刊
Cancers2023 Jan 15
原文标识
PubMed 36672477 · DOI 10.3390/cancers15020528