Exploration of the Tumour Biological Significance of PCLO in Gastric Cancer: Results from a Large Central European Cohort.

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-11-07 DOI:10.1159/000534889

Maximilian Bernhardt, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken

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引用次数: 0

Abstract

Introduction: A recent multiregional whole-exome sequencing of 48 tumour samples from 9 gastric adenocarcinomas discovered PCLO mutations in 23 (47.9%) tumour samples. Based on that unexpected high prevalence of PCLO mutations, we hypothesized a tumour biological significance of PCLO in gastric cancer (GC).

Methods: Tumour samples (whole tissue sections) obtained from 466 patients resected for therapy-naive GC were stained with an anti-PCLO antibody. The histoscore for tumour cells and the presence of immunostaining of stromal cells and tumour vessels was documented for each case. An algorithm for PCLO immunopositivity was formed and correlated with clinicopathological patient characteristics.

Results: 175 GCs were classified as PCLO positive within tumour cells, and 291 as negative. Stromal cells were positive for PCLO in 106 cases and tumour vessels in 84. PCLO-positive GCs more often showed an intestinal phenotype, a lower T category and were more commonly associated with Helicobacter pylori infection. A separate analysis of PCLO expression in intestinal and diffuse type GCs, respectively, showed no significant correlations. Patients with PCLO negative/low tumour cells showed a shortened overall (14.0 ± 1.4 vs. 16.0 ± 1.8 months) and tumour-specific survival (15.0 ± 1.6 months vs. 17.9 ± 3.6). Comparison of PCLOs genotype with its phenotype in 48 tumour samples obtained from nine cases showed no direct correlations with missense mutations.

Conclusion: Our data provide evidence that PCLO is differentially expressed in GC and might delay tumour progression.

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探讨PCLO在癌症中的肿瘤生物学意义-来自中欧大型队列的结果。

引言：最近对来自9个胃癌的48个肿瘤样本进行的多区域全外显子组测序发现，23个（47.9%）肿瘤样本中存在PCLO突变。基于PCLO突变的意外高患病率，我们假设PCLO在癌症（GC）中的肿瘤生物学意义。方法：用抗PCLO抗体对466例接受治疗的胃癌患者的肿瘤样本（全组织切片）进行染色。记录每个病例的肿瘤细胞的组织分数以及基质细胞和肿瘤血管的免疫染色。形成了PCLO免疫阳性的算法，并将其与临床病理患者特征相关联。结果：175个GC在肿瘤细胞中被归类为PCLO阳性，291个GC被归类为阴性。基质细胞PCLO阳性106例，肿瘤血管阳性84例。PCLO阳性GC更经常表现出肠道表型，一种较低的T类，并且更常见地与幽门螺杆菌感染有关。分别对肠型和弥漫型GC中PCLO表达的单独分析显示，没有显著相关性。PCLO阴性/低肿瘤细胞患者的总生存期缩短（14.0±1.4个月vs.16.0±1.8个月），肿瘤特异性生存期（15.0±1.6个月vs.17.9±3.6个月）。在9例患者的48个肿瘤样本中，PCLO的基因型与其表型的比较显示，与错义突变没有直接相关性。讨论/结论：我们的数据提供了证据，证明PCLO在GC中差异表达，并可能延缓肿瘤进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.