Background: Tumor mutational burden (TMB) has been identified as one of the predictors for the response to anti-programmed cell death-1 (anti-PD-1) antibody therapy and reported to correlate with smoking history in lung adenocarcinoma. However, in squamous cell carcinoma of the lung, the association between TMB and clinicopathological background factors, such as smoking history, has not been reported, including in our previous study. The mutational signature is a tool to identify the mutagens that are contributing to the mutational spectrum of a tumor by investigating the pattern of DNA changes. Here, we analyzed the mutational signature in lung squamous cell carcinoma to identify mutagens affecting the TMB.
Methods: Seven representative mutational signatures including signature 7 (SI7) [ultraviolet (UV)-related], SI4 (smoking), SI6/15 [mismatch repair (MMR)], SI2/13 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)], and SI5 (clock-like) were analyzed in Japanese patients with lung squamous cell carcinoma (n=67) using data generated by next-generation sequencing consisting of a 415-gene panel. The relationships between signatures and clinico-pathological data including TMB and programmed death-ligand 1 (PD-L1) expression were analyzed.
Results: Although the reconstructed mutational counts were small with targeted sequencing (median: 30.1, range: 13.3-98.7), the distributions of signatures were comparable among samples, with 56 cases containing more than four signatures. The smoking-related SI4 was found in 45 cases and was significantly related with pack-year index (PYI) (P=0.026). The reconstructed mutation counts were highly correlated with SI4 (r=0.51, P<0.0001), whereas the correlation was weak with SI6/15 (MMR-related) and SI2/13 (APOBEC-related). There was no mutational signature related with PD-L1 expression. Some patients exhibited unique signatures; the patient with the highest mutational counts had a MMR signature, and another patient with a prominent UV signature had occupational exposure to UV, as he was employed as a neon sign engineer.
Conclusions: Mutational signatures can predict the cause of lung squamous cell carcinoma. Tobacco smoking is the mutagen most related with TMB.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947495 | PMC |
| http://dx.doi.org/10.21037/jtd-20-2602 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into morphology of the 'columnar epithelium' within the female reproductive system of brachyuran crabs.
Arthropod Struct Dev
January 2025
Zoological Museum, University of Kiel, Hegewischstrasse 3, 24105, Kiel, Germany.
The objective of this study is to gain a better understanding of the not well understood egg-transportation mechanisms through the female reproductive systems of crabs. For this, Carcinus maenas was chosen as a model to study the cuticular epithelium underlying the cuticle of the vagina and the ventral seminal receptacle. This cuticular epithelium is investigated by performing histochemical and ultrastructural analyses of the epithelial cells.
View Article and Find Full Text PDFExercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.
Proc Natl Acad Sci U S A
January 2025
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-wk exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD).
View Article and Find Full Text PDFUnseen Threats: The Long-term Impact of PET-Microplastics on Development of Male Reproductive Over a Lifetime.
Adv Sci (Weinh)
January 2025
Department of Food Science and Nutrition, Pukyong National University, Busan, 48513, Republic of Korea.
The physical abrasion of plastics from simple everyday entered the food chain, with associated risks recently emphasized. Although many studies have reported the adverse effects of microplastics (MPs) on human, the reproductive implications of continuous exposure to physically abraded polyethylene terephthalate (PET)-MPs remain unexplored. Ingestion of physically abraded PET-MPs (size range: 50-100 µm) in mice from 5 to 34 weeks of age at an annual intake relevant dose of MPs (5 mg week) significantly impaired male reproductive function.
View Article and Find Full Text PDFMesenchymal stem cell-derived exosome and liposome hybrids as transfection nanocarriers of Cas9-GFP plasmid to HEK293T cells.
PLoS One
January 2025
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Exosomes are natural membrane-enclosed nanovesicles (30-150 nm) involved in cell-cell communication. Recently, they have garnered considerable interest as nanocarriers for the controlled transfer of therapeutic agents to cells. Here, exosomes were derived from bone marrow mesenchymal stem cells using three different isolation methods.
View Article and Find Full Text PDFScale-Up of Human Amniotic Epithelial Cells Through Regulation of Epithelial-Mesenchymal Plasticity Under Defined Conditions.
Adv Sci (Weinh)
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, P. R. China.
Human amniotic epithelial cells (hAECs) have shown excellent efficacy in clinical research and have prospective applications in the treatment of many diseases. However, the properties of the hAECs and their proliferative mechanisms remain unclear. Here, single-cell RNA sequencing (scRNA-seq) is performed on hAECs obtained from amniotic tissues at different gestational ages and passages during in vitro culture.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!