Evaluation of the roles and regulatory mechanisms of PD-1 target molecules in NSCLC progression

Yun-Qiang Zhang1, Ye Yuan2, Jun Zhang2

  • 1Department of Thoracic Surgery, Beilun District People's Hospital of Ningbo, Ningbo, China.

Abstract

Insights

Programmed cell death protein 1 (PD-1) therapy improves non-small cell lung cancer (NSCLC) prognosis. PD-1 target molecules, particularly HIST1H2BH and PLK1, are key prognostic biomarkers for NSCLC patients.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Targeted programmed cell death protein 1 (PD-1) therapy offers improved long-term outcomes for non-small cell lung cancer (NSCLC) patients.
  • The precise role of PD-1 targets in NSCLC progression requires further elucidation.

Purpose of the Study:

  • To identify differentially expressed genes (DEGs) associated with PD-1 therapy in NSCLC.
  • To elucidate the functional mechanisms of PD-1 target molecules.
  • To develop a prognostic risk model for NSCLC patients based on PD-1 target molecules.

Main Methods:

  • Analysis of DEGs in blood and tissue samples from NSCLC patients treated with nivolumab.
  • Utilized GEO2R, TCGA database, Gene Ontology (GO), and KEGG pathway analysis.
  • Constructed a protein-protein interaction (PPI) network and employed COX regression and survival analysis to build a prognostic risk model and nomogram.

Main Results:

  • Identified 64 DEGs in blood and 48 DEGs in NSCLC tissues post-nivolumab treatment.
  • PD-1 target molecules are implicated in cell proliferation, DNA replication, and cell cycle regulation.
  • HIST1H2BH and PLK1 were identified as independent prognostic factors, overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and correlated with overall survival (OS) and progression-free survival (PFS).

Conclusions:

  • A risk model incorporating PD-1 target molecules effectively assesses NSCLC prognosis.
  • HIST1H2BH and PLK1 demonstrate potential as valuable prognostic biomarkers for NSCLC.

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.7K
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...
4.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.1K