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胃腺癌中 PYCR1、BANF1 和 STARD8 的表达:一项临床病理、预后和免疫组织化学研究。

PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study.

机构信息

Departments of Pathology.

Clinical Oncology and Nuclear Medicine.

出版信息

Appl Immunohistochem Mol Morphol. 2024 Feb 1;32(2):102-110. doi: 10.1097/PAI.0000000000001173. Epub 2023 Nov 20.

Abstract

BACKGROUND

It will be important to understand the molecular pathways of gastric cancer (GC) occurrence and progression, thus detecting predictive and prognostic biomarkers of GC. Pyrroline-5-carboxylate reductase 1 (PYCR1) was upregulated in many cancers, suggesting its possible roles in carcinogenesis and tumor metastases. Barrier-of-autointegration factor 1 (BANF1) is a protein family that plays essential roles in maintaining the integrity of an intact cellular genome. Rho-GTPs are molecular switches that control many signal transduction pathways in normal cells, including 3 subgroups from 1 to 3 (DLC1-3). DLC-3, known as StAR-related lipid transfer domain protein 8 (STARD8), and its role in cancers were not sufficiently studied. The study aimed to investigate the significance of PYCR1, BANF1, and STARD8 protein expression in GC tissues and normal gastric mucosa retrieved from patients with GC to detect prognostic roles of expression.

PATIENTS AND METHODS

Specimens were collected from 100 patients with gastric carcinoma. After the application of the inclusion criteria of the study, we prepared 100 paraffin blocks from samples of the 100 included patients; each block included samples from gastric carcinoma and adjacent non-neoplastic gastric mucosa. We assessed the expression of PYCR1, BANF1, and STARD8 using immunohistochemistry in all studied samples. We followed patients for the detection of disease progression and survival rates. We correlate PYCR1, BANF1, and STARD8 expression with clinical, pathologic, and prognostic parameters.

RESULTS

Overexpression of PYCR1 and BANF1 and decreased expression of STARD8 was found in gastric carcinoma tissues than adjacent non-neoplastic gastric mucosa ( P <0.001), and was positively associated with high grade ( P =0.006), depth of tumor invasion, presence of lymph nodes metastases and advanced stage ( P =0.001), high incidence of GC progression, recurrence, unfavorable disease-free survival ( P =0.003) and unfavorable overall survival rates ( P <0.001). Thus, it was revealed that; in univariate and multivariate analyses, levels of PYCR1, BANF1, and STARD8 are associated with the overall survival rate of GC patients.

CONCLUSIONS

We showed that overexpression of PYCR1 and BANF1 and decreased expression of STARD8 in GC tissues was associated with poor prognosis and GC progression.

摘要

背景

了解胃癌(GC)发生和进展的分子途径非常重要,因此需要检测 GC 的预测和预后生物标志物。吡咯啉-5-羧酸还原酶 1(PYCR1)在许多癌症中上调,表明其在致癌和肿瘤转移中可能发挥作用。整合素屏障因子 1(BANF1)是一个蛋白家族,在维持完整细胞基因组的完整性方面发挥着重要作用。Rho-GTP 是分子开关,可控制正常细胞中的许多信号转导途径,包括 1 到 3 组(DLC1-3)。DLC-3 被称为星相关脂转移结构域蛋白 8(STARD8),其在癌症中的作用尚未得到充分研究。本研究旨在探讨 GC 组织中 PYCR1、BANF1 和 STARD8 蛋白表达的意义,以检测其表达的预后作用。

患者和方法

从 100 例胃癌患者中收集标本。在应用本研究纳入标准后,我们从 100 例纳入患者的样本中制备了 100 个石蜡块;每个块均包含来自胃癌和相邻非肿瘤性胃粘膜的样本。我们使用免疫组织化学法评估所有研究样本中 PYCR1、BANF1 和 STARD8 的表达。我们对患者进行了疾病进展和生存率的检测。我们将 PYCR1、BANF1 和 STARD8 的表达与临床、病理和预后参数相关联。

结果

与相邻非肿瘤性胃粘膜相比,PYCR1 和 BANF1 的过表达和 STARD8 的表达降低在胃癌组织中发现(P<0.001),并且与高分级(P=0.006)、肿瘤浸润深度、淋巴结转移和晚期(P=0.001)、GC 进展、复发、不良无病生存率(P=0.003)和不良总生存率(P<0.001)呈正相关。因此,在单变量和多变量分析中,PYCR1、BANF1 和 STARD8 的水平与 GC 患者的总生存率相关。

结论

我们表明,GC 组织中 PYCR1 和 BANF1 的过表达和 STARD8 的表达降低与不良预后和 GC 进展有关。

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