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非小细胞肺癌患者 HRAS 和 KRAS 基因表达的临床意义——初步发现。

Clinical significance of HRAS and KRAS genes expression in patients with non-small-cell lung cancer - preliminary findings.

机构信息

Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Cathedral of Laboratory and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151, Lodz, Poland.

Department of Thoracic Surgery, Memorial Copernicus Hospital, Medical University of Lodz, Lodz, Poland.

出版信息

BMC Cancer. 2021 Feb 6;21(1):130. doi: 10.1186/s12885-021-07858-w.

Abstract

BACKGROUND

The RAS family protooncogenes, including KRAS, NRAS and HRAS, encode proteins responsible for the regulation of growth, differentiation and survival of many cell types. The HRAS and KRAS oncogene mutations are well defined, however, the clinical significance of RAS expressions in non-small-cell lung cancer (NSCLC) is still uncertain.

METHODS

A total of 39 whole blood samples of NSCLC (the investigated group), collected at three points of time: at the time of diagnosis, 100 days and 1 year after the surgery as well as 35 tissue samples obtained during the surgery were included in this study. HRAS and KRAS genes mRNA expression were assessed using quantitative real-time polymerase chain reaction techniques.

RESULTS

Increased relative HRAS mRNA level in blood was found significantly more frequently in the group of smokers (p = 0.008). Patients with squamous cell carcinoma subtypes of NSCLC were more likely to show an overexpression of HRAS gene in blood, but not statistically significant (p = 0.065). In tumor tissue overexpression of HRAS gene was associated with adenocarcinoma subtype (p = 0.049). No statistically significant associations were found for the expression of KRAS with any clinicopathological parameters, except the age of patients, within the study. There were no differences between the relative HRAS and KRAS genes expression levels in blood samples taken from the same patients during the 3 observation points, as well as between blood collected from patients before surgery and tissue samples obtained during operation.

CONCLUSION

The potential associations between high HRAS expression levels, age, smoking status and histological type of cancer were observed, which emphasizes the need for further study of the RAS family. Therefore, subsequent research involving larger numbers of patients and a longer follow-up, as well as multicenter study are necessary to confirm our findings.

摘要

背景

RAS 家族原癌基因,包括 KRAS、NRAS 和 HRAS,编码负责调节多种细胞类型生长、分化和存活的蛋白质。HRAS 和 KRAS 癌基因突变已得到明确界定,然而,RAS 表达在非小细胞肺癌(NSCLC)中的临床意义仍不确定。

方法

本研究共纳入 39 例 NSCLC 全血样本(研究组),分别在诊断时、手术后 100 天和 1 年以及手术期间采集 35 份组织样本。采用实时定量聚合酶链反应技术检测 HRAS 和 KRAS 基因 mRNA 表达。

结果

发现吸烟者血液中 HRAS mRNA 水平升高的相对比例显著更高(p=0.008)。非小细胞肺癌鳞状细胞癌亚型患者血液中 HRAS 基因过表达的可能性更大,但无统计学意义(p=0.065)。在肿瘤组织中,HRAS 基因的过表达与腺癌亚型相关(p=0.049)。除患者年龄外,KRAS 表达与任何临床病理参数均无统计学显著相关性。在 3 个观察点采集的相同患者的血液样本中,以及在手术前采集的血液样本与手术期间获得的组织样本中,HRAS 和 KRAS 基因的相对表达水平无差异。

结论

观察到 HRAS 高表达水平、年龄、吸烟状态和癌症组织学类型之间存在潜在关联,这强调了需要进一步研究 RAS 家族。因此,需要进行后续研究,包括纳入更多患者和更长随访时间以及多中心研究,以证实我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d4/7866659/5516b5d10ae1/12885_2021_7858_Fig1_HTML.jpg

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