Identification of Novel Stemness-based Subtypes and Construction of a Prognostic Risk Model for Patients with Lung Squamous Cell Carcinoma

  • Authors: Shen F.1, Li F.2, Ma Y.3, Song X.1, Guo W.1
  • Affiliations:
    1. Department of Respiratory Medicine, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University
    2. Department of thoracic surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University,
    3. Department of thoracic surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University
  • Issue: Vol 19, No 3 (2024)
  • Pages: 400-416
  • Section: Medicine
  • URL: https://rjsocmed.com/1574-888X/article/view/645774
  • DOI: https://doi.org/10.2174/1574888X18666230714142835
  • ID: 645774

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Full Text

Abstract

Background:Although cancer stem cells (CSCs) contribute to tumorigenesis, progression, and drug resistance, stemness-based classification and prognostic signatures of lung squamous cell carcinoma (LUSC) remain unclarified. This study attempted to identify stemness-based subtypes and develop a prognostic risk model for LUSC.

Methods:Based on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Progenitor Cell Biology Consortium (PCBC), mRNA expression-based stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR) algorithm. A weighted gene coexpression network (WGCNA) was employed to identify stemness subtypes. Differences in mutation, clinical characteristics, immune cell infiltration, and antitumor therapy responses were determined. We constructed a prognostic risk model, followed by validations in GEO cohort, pan-cancer and immunotherapy datasets.

Results:LUSC patients with subtype C2 had a better prognosis, manifested by higher mRNAsi, higher tumor protein 53 (TP53) and Titin (TTN) mutation frequencies, lower immune scores and decreased immune checkpoints. Patients with subtype C2 were more sensitive to Imatinib, Pyrimethamine, and Paclitaxel therapy, whereas those with subtype C1 were more sensitive to Sunitinib, Saracatinib, and Dasatinib. Moreover, we constructed stemness-based signatures using seven genes (BMI1, CCDC51, CTNS, EIF1AX, FAM43A, THBD, and TRIM68) and found high-risk patients had a poorer prognosis in the TCGA cohort. Similar results were found in the GEO cohort. We verified the good performance of risk scores in prognosis prediction and therapy responses.

Conclusion:The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.

About the authors

Fangfang Shen

Department of Respiratory Medicine, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University

Email: info@benthamscience.net

Feng Li

Department of thoracic surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University,

Email: info@benthamscience.net

Yong Ma

Department of thoracic surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University

Email: info@benthamscience.net

Xia Song

Department of Respiratory Medicine, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University

Author for correspondence.
Email: info@benthamscience.net

Wei Guo

Department of Respiratory Medicine, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital,, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University

Author for correspondence.
Email: info@benthamscience.net

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