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

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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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12885-021-07858-w.

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Most cited references 26

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Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Kenneth Livak, Thomas D. Schmittgen (2001)

The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).

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Progress and prospects of early detection in lung cancer

Sean Blandin Knight, Phil Crosbie, Haval Balata … (2017)

Lung cancer is the leading cause of cancer-related death in the world. It is broadly divided into small cell (SCLC, approx. 15% cases) and non-small cell lung cancer (NSCLC, approx. 85% cases). The main histological subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma, with the presence of specific DNA mutations allowing further molecular stratification. If identified at an early stage, surgical resection of NSCLC offers a favourable prognosis, with published case series reporting 5-year survival rates of up to 70% for small, localized tumours (stage I). However, most patients (approx. 75%) have advanced disease at the time of diagnosis (stage III/IV) and despite significant developments in the oncological management of late stage lung cancer over recent years, survival remains poor. In 2014, the UK Office for National Statistics reported that patients diagnosed with distant metastatic disease (stage IV) had a 1-year survival rate of just 15–19% compared with 81–85% for stage I.

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RAS isoforms and mutations in cancer at a glance.

G. Aaron Hobbs, Channing J. Der, Kent Rossman (2016)

RAS proteins (KRAS4A, KRAS4B, NRAS and HRAS) function as GDP-GTP-regulated binary on-off switches, which regulate cytoplasmic signaling networks that control diverse normal cellular processes. Gain-of-function missense mutations in RAS genes are found in ∼25% of human cancers, prompting interest in identifying anti-RAS therapeutic strategies for cancer treatment. However, despite more than three decades of intense effort, no anti-RAS therapies have reached clinical application. Contributing to this failure has been an underestimation of the complexities of RAS. First, there is now appreciation that the four human RAS proteins are not functionally identical. Second, with >130 different missense mutations found in cancer, there is an emerging view that there are mutation-specific consequences on RAS structure, biochemistry and biology, and mutation-selective therapeutic strategies are needed. In this Cell Science at a Glance article and accompanying poster, we provide a snapshot of the differences between RAS isoforms and mutations, as well as the current status of anti-RAS drug-discovery efforts.

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Author and article information

Contributors

Milena Pązik:

ORCID: http://orcid.org/0000-0003-0965-4513

milena.pazik@umed.lodz.pl

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 6 February 2021

Publication date PMC-release: 6 February 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 130

Affiliations

[1 ]GRID grid.8267.b, ISNI 0000 0001 2165 3025, 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

[2 ]GRID grid.8267.b, ISNI 0000 0001 2165 3025, Department of Thoracic Surgery, Memorial Copernicus Hospital, , Medical University of Lodz, ; Lodz, Poland

Author information

Milena Pązik http://orcid.org/0000-0003-0965-4513

Article

Publisher ID: 7858

DOI: 10.1186/s12885-021-07858-w

PMC ID: 7866659

PubMed ID: 33549031

SO-VID: f8496fdf-f029-4036-ac63-2fcb12cd51b6

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 22 October 2020

Date accepted : 31 January 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100005888, Uniwersytet Medyczny w Lodzi;

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lung cancer,nsclc,hras,kras,expression

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lung cancer, nsclc, hras, kras, expression

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

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Abstract

Background

Methods

Results

Conclusion

Supplementary Information

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Karger: Oncology

Most cited references 26

Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Progress and prospects of early detection in lung cancer

RAS isoforms and mutations in cancer at a glance.

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Cited by 7

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