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INHBA 过表达与宫颈癌病理特征、抗肿瘤免疫反应及临床预后的相关性。

Correlation of INHBA Overexpression with Pathological Features, Antitumor Immune Response and Clinical Prognosis in Cervical Cancer.

机构信息

Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.

Department of Pathology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang 621000, China.

出版信息

Medicina (Kaunas). 2023 Mar 2;59(3):495. doi: 10.3390/medicina59030495.

DOI:10.3390/medicina59030495
PMID:36984496
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10051788/
Abstract

: Cervical cancer (CC) is a malignant tumor occurring in the cervical epithelium, which is one of the most common cancer-caused deaths in females. Inhibin β A (INHBA) is the most widely expressed biomarker of the transforming growth factor-β (TGF-β) family in tumor cells, and has predictive value for tumor development and prognosis. In this study, the expression of INHBA in CC tissue was examined to analyze the relationship between INHBA expression and pathological characteristics, anti-tumor immune response and clinical prognosis of CC. In addition, the factors affecting the prognosis of CC patients were explored. : 84 patients with CC, who underwent surgical resection in our hospital from March 2016 to August 2017, were retrospectively picked. The tumor tissues and normal adjacent tissues of patients with CC were collected, and the expression of INHBA in CC tissues and adjacent tissues was detected using immunohistochemistry (IHC). The relationship between INHBA expression and clinicopathological characteristics of CC patients was analyzed. The relationship between INHBA expression and clinical prognosis was analyzed using the Kaplan-Meier (K-M) survival curve. The levels of anti-tumor immune-response-related factors (interferon-γ (IFN-γ), interleukin-10 (IL-10), tumor necrosis factor- α (TNF-α) and IL-2) were evaluated in patients with negative and positive expressions of INHBA. The patients were followed up for 60 months and were graded as a good prognosis group and poor prognosis group according to whether the patients died or had recurrence and metastasis. Relevant factors affecting the prognosis of the patients were analyzed. INHBA was localized in the cytoplasm of cancer tissues. The positive expression rate in cancer tissues was 67.86%, which was much higher than the 28.57% in normal adjacent tissues ( < 0.05). Expression of INHBA was closely correlated with Federation of Gynecology and Obstetrics (FIGO) staging, differentiation and lymph node metastasis ( < 0.05). Compared with INHBA-negative expression group, the contents of IFN-γ, TNF-α and IL-2 were much lower, while the level of IL-10 was strongly elevated in the INHBA-positive expression group ( < 0.01). Eighty-four patients with CC were followed up for 36 months. The K-M survival curve showed that the patients with a positive expression of INHBA had a significantly shorter survival period than the patients with a negative expression of INHBA ( < 0.05). There were significant differences in FIGO staging, differentiation, lymph node metastasis and INHBA expression between patients with a good prognosis and poor prognosis ( < 0.05). Logistic regression analysis showed that FIGO stage, differentiation degree, lymph node metastasis and INHBA were the factors influencing the poor prognosis of patients with CC ( < 0.05). The abnormally high expression of INHBA in patients with CC was related to the pathological characteristics, anti-tumor immune response and survival time, and leaded to a poor prognosis. It was speculated that INHBA exerted an important reference role in tumor invasion and clinical prognosis evaluation, which could act as a new target for anti-tumor treatment of CC.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/b112bcaf000b/medicina-59-00495-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/c3f6f95f89f5/medicina-59-00495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/b36239453e8e/medicina-59-00495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/379a3fa8bfbc/medicina-59-00495-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/b112bcaf000b/medicina-59-00495-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/c3f6f95f89f5/medicina-59-00495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/b36239453e8e/medicina-59-00495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/379a3fa8bfbc/medicina-59-00495-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d4/10051788/b112bcaf000b/medicina-59-00495-g004.jpg
摘要

宫颈癌(CC)是发生在宫颈上皮的恶性肿瘤,是女性癌症死亡的主要原因之一。抑制素β A(INHBA)是肿瘤细胞中转化生长因子-β(TGF-β)家族中表达最广泛的生物标志物,对肿瘤的发展和预后具有预测价值。本研究检测了 INHBA 在 CC 组织中的表达,分析了 INHBA 表达与 CC 病理特征、抗肿瘤免疫反应和临床预后的关系。此外,还探讨了影响 CC 患者预后的因素。

选取我院 2016 年 3 月至 2017 年 8 月行手术切除的 84 例 CC 患者为研究对象。收集患者 CC 组织及癌旁正常组织,采用免疫组化(IHC)法检测 CC 组织及癌旁组织中 INHBA 的表达,分析 INHBA 表达与 CC 患者临床病理特征的关系。采用 Kaplan-Meier(K-M)生存曲线分析 INHBA 表达与临床预后的关系。评估 INHBA 阴性和阳性表达患者的抗肿瘤免疫反应相关因子(干扰素-γ(IFN-γ)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)和白细胞介素-2(IL-2))水平。对患者进行 60 个月随访,根据患者是否死亡或复发转移分为预后良好组和预后不良组。分析影响患者预后的相关因素。

INHBA 定位于癌组织细胞质中。癌组织阳性表达率为 67.86%,明显高于癌旁正常组织的 28.57%(<0.05)。INHBA 表达与妇产科联合会(FIGO)分期、分化程度及淋巴结转移密切相关(<0.05)。与 INHBA 阴性表达组比较,INHBA 阳性表达组 IFN-γ、TNF-α 和 IL-2 含量明显降低,IL-10 水平明显升高(<0.01)。84 例 CC 患者随访 36 个月。K-M 生存曲线显示,INHBA 阳性表达患者的生存期明显短于 INHBA 阴性表达患者(<0.05)。预后良好组与预后不良组在 FIGO 分期、分化程度、淋巴结转移和 INHBA 表达方面比较,差异有统计学意义(<0.05)。Logistic 回归分析显示,FIGO 分期、分化程度、淋巴结转移和 INHBA 是影响 CC 患者预后不良的因素(<0.05)。

CC 患者 INHBA 异常高表达与病理特征、抗肿瘤免疫反应及生存时间有关,导致预后不良。推测 INHBA 对肿瘤侵袭及临床预后评估具有重要的参考作用,可作为 CC 抗肿瘤治疗的新靶点。

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