Related Experiment Video

Updated: Dec 11, 2025

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.3K

Oncogene HSPH1 modulated by the rs2280059 genetic variant diminishes EGFR-TKIs efficiency in advanced lung

Yankang Li1,2, Nasha Zhang1,2,3, Li Zhang4

  • 1Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

Carcinogenesis
|August 21, 2020
PubMed

Insights

A specific gene variation (HSPH1 SNP rs2280059) impacts non-small-cell lung cancer (NSCLC) patient survival during EGFR-TKI therapy. This finding may improve treatment outcomes and patient assessment.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy benefits many advanced non-small-cell lung cancer (NSCLC) patients with mutant EGFR.
  • However, some patients exhibit limited or no response to EGFR-TKI treatment, suggesting other factors influence treatment efficacy.
  • Germline variations, including single-nucleotide polymorphisms (SNPs), are implicated in disease progression and treatment response.

Purpose of the Study:

  • To investigate the hypothesis that functional Heat Shock Protein 1 (HSPH1) single-nucleotide polymorphisms (SNPs) affect gene expression and influence the prognosis of NSCLC patients undergoing EGFR-TKI therapy.
  • To examine the impact of HSPH1 SNPs on NSCLC patient survival in independent cohorts treated with EGFR-TKIs.

Main Methods:

  • Systematic examination of HSPH1 SNPs in two independent cohorts comprising 319 stage IIIB/IV NSCLC patients treated with EGFR-TKIs.
  • In vitro and in vivo assays to elucidate the functional impact of the rs2280059 polymorphism on HSPH1 promoter activity.
  • Assessment of the effect of HSPH1 silencing on the efficacy of gefitinib in NSCLC cells.

Main Results:

  • The promoter rs2280059 polymorphism was significantly associated with patient survival in both independent cohorts.
  • The G allele of rs2280059 demonstrated a higher capacity to drive HSPH1 promoter activity.
  • Silencing HSPH1 expression significantly enhanced the antineoplastic effects of gefitinib on NSCLC cells.

Conclusions:

  • The HSPH1 gene, particularly the rs2280059 polymorphism, plays a significant role in the prognosis of NSCLC patients treated with EGFR-TKIs.
  • These findings suggest that HSPH1 may serve as a potential biomarker for predicting treatment response and guiding clinical decisions.
  • Further understanding of HSPH1's role could lead to improved treatment strategies and outcome assessments for NSCLC patients undergoing EGFR-TKI therapy.

More Related Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.0K
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer07:59

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

1.5K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.9K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
17.7K