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结直肠癌中前列腺素内过氧化物合酶-2基因低表达可能预示较差的生存率。

Low prostaglandin-endoperoxide synthase-2 gene expression in colorectal carcinomas may predict poorer survival.

作者信息

Ezenkwa Uchenna Simon, Omenai Sebastian Anebuokhae, Iyapo Oluwadamilare, Ezekekwu Chinedu Anthony, Adetona Adesoji E, Akunwata Chima Uzoma, Ale Ayotunde Oladunmi, Ebili Henry Okwuchukwu

机构信息

Department of Histopathology, Federal University of Health Sciences Azare, Azare 751101, Bauchi, Nigeria.

Department of Pathology, Federal Medical Centre Azare, Azare 751101, Bauchi, Nigeria.

出版信息

Ecancermedicalscience. 2024 Dec 6;18:1814. doi: 10.3332/ecancer.2024.1814. eCollection 2024.

Abstract

INTRODUCTION

Prostaglandin-endoperoxide synthase-2 (ptgs2), otherwise called Cyclooxygenase 2, is overexpressed in colorectal carcinoma (CRC) compared to normal tissues. However, the impact of differential expression among ptgs2-positive tumours on CRC prognosis has not been well investigated. By sub-stratifying positive tumour expression, this study determined its potential influence on patients' outcomes.

METHODS

The Cancer Genome Atlas database was explored to determine CRC cases with RNA-Sequence (RNA-Seq) transcript data and matched clinicopathological data alongside gene copy number variation and methylation status. Descriptive, chi-square, Fisher exact, Linear-by-Linear associations, logistic and Kaplan-Meier statistics were used to determine proportions, associations, predictors and survival between ptgs2 and tumour parameters using Statistical Package for Social Sciences version 20. Two-tailed -value <0.05 was accepted as statistically significant.

RESULTS

There were 534 CRC classified predominantly as adenocarcinoma not otherwise specified (86.3%) and mucinous carcinoma (12.4) histologically included in this study. Marker (ptgs2) expression ranged from 0.02 FPKM-131.89 FPKM, (Median 1.4 FPKM). The majority of the cases (53.4%) were diagnosed at an early stage and showed high ptgs2 RNA-Sequence (RNA-seq) expression in 51.5% (275/534). Significant associations were seen between ptgs2 expression and histological subtype ( < 0.001), lymphovascular invasion (p = 0.013), pN2 stage (> 6 positive lymph nodes) ( = 0.011) and American Joint Committee on Cancer Staging stage ( = 0.028), and these all had lower ptgs2 expression. On regression analysis, histological differentiation emerged as a predictor of ptgs2 expression (Odds ratio 2.749, 95% confidence interval 1.479-5.108, < 0.001). Also, gene methylation was associated with reduced ptgs2 expression. Overall survival was significantly inferior among individuals with low ptgs2 tumours ( = 0.018) while that for disease-free survival was non-significant ( = 0.327).

CONCLUSION

CRCs with low ptgs2 transcripts are associated with poorer survival. This finding suggests a need for closer follow up and tailored adjuvant therapy for these patients.

摘要

引言

前列腺素内过氧化物合酶-2(ptgs2),又称环氧化酶2,与正常组织相比,在结直肠癌(CRC)中过度表达。然而,ptgs2阳性肿瘤之间的差异表达对CRC预后的影响尚未得到充分研究。通过对肿瘤阳性表达进行亚分层,本研究确定了其对患者预后的潜在影响。

方法

利用癌症基因组图谱数据库确定具有RNA序列(RNA-Seq)转录数据以及匹配的临床病理数据、基因拷贝数变异和甲基化状态的CRC病例。使用社会科学统计软件包第20版中的描述性统计、卡方检验、Fisher精确检验、线性-线性关联、逻辑回归和Kaplan-Meier统计来确定ptgs2与肿瘤参数之间的比例、关联、预测因素和生存率。双侧P值<0.05被认为具有统计学意义。

结果

本研究纳入了534例主要组织学分类为未另行规定的腺癌(86.3%)和黏液癌(12.4%)的CRC。标志物(ptgs2)表达范围为0.02 FPKM - 131.89 FPKM,(中位数1.4 FPKM)。大多数病例(53.4%)在早期被诊断出来,51.5%(275/534)的病例显示ptgs2 RNA序列(RNA-seq)高表达。ptgs2表达与组织学亚型(P<0.001)、淋巴管浸润(P = 0.013)、pN2期(>6个阳性淋巴结)(P = 0.011)和美国癌症联合委员会分期(P = 0.028)之间存在显著关联,且这些情况的ptgs2表达均较低。回归分析显示,组织学分化是ptgs2表达的预测因素(比值比2.749,95%置信区间1.479 - 5.108,P<0.001)。此外,基因甲基化与ptgs2表达降低有关。ptgs2低表达肿瘤患者的总生存期显著较差(P = 0.018),而无病生存期则无显著差异(P = 0.327)。

结论

ptgs2转录本低的CRC与较差的生存率相关。这一发现表明需要对这些患者进行更密切的随访和量身定制的辅助治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcfe/11959140/c715f8d791d3/can-18-1814fig1.jpg

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