Page 18 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Single-cell sequencing for lung cancer

bisphosphate 3-kinase catalytic subunit delta (PIK3CD), 4.3. Single-cell sequencing in drug resistance and
and ubiquinol-cytochrome c reductase, complex III individualized therapy in lung cancer
subunit X (UQCR10) and PD-1 expression, suggesting Acquired drug resistance is a major factor contributing
their potential as predictive markers for pembrolizumab to poor prognosis and survival outcomes in cancer. 78,79
efficacy in PD-L1-negative squamous lung cancer. In Disease recurrence is also caused by drug resistance, which
another study, Yudi Hu et al. investigated the changes can be due to genetic or epigenetic changes, modifications
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in smoking on T cells in primary NSCLC patients by in drug targets, inhibition of apoptosis, increased drug
integrating single-cell RNA-seq and bulk RNA-seq data. efflux, and other cellular and molecular mechanisms. 80,81
The results showed that smoking induced high expression Single-cell sequencing helps to understand the
of metallopeptidase domain 12 (ADAM12) in tumor- mechanisms of drug resistance in lung cancer. Through
specific Tregs in untreated NSCLC patients, indicating scRNA-seq and scATAC-seq analysis of cell line models
ADAM12 as a potential biomarker and therapeutic target. and clinical specimens, Yukie Kashima identified CD74
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Ruan et al. found that the expression of CEA cell adhesion as an important factor in the transition of tumor cells from
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molecule 6 (CEACAM6), secretoglobin family 3A member a naïve to a drug-tolerant state. CD74 upregulation confers
2 (SCGB3A2), and complement C3 (C3) was significantly resistance to the epidermal growth factor receptor tyrosine
elevated in tumor cells within the cerebrospinal fluid of kinase inhibitor (EGFR-TKI) osimertinib and blocks
patients with soft meningeal metastases from LUAD, apoptosis, enabling tumor regrowth. Salcher S focused
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suggesting these molecules as potential markers of tumor on tissue-resident neutrophils (TRNs) by analyzing
metastasis. A recent study integrated scRNA-seq and 1,283,972 single cells integrated from 556 samples and
lipidomics to develop a lung cancer artificial intelligence
detector (LCAID) v2.0, a lipid-targeted detection method 318 patients. The study revealed that genetic markers
for early lung cancer diagnosis. scRNA-seq revealed lipid derived from TRNs were linked to treatment failure with
anti-programmed cell death ligand 1 (PD-L1) therapy. In
metabolism dysregulation in tumor cells and identified addition, researchers generated CTC-derived xenografts
nine lipid biomarkers through machine learning. Its from patients with SCLC and performed single-cell RNA
accuracy and high specificity make it a valuable tool for
early detection and large-scale screening of high-risk sequencing on both chemoresistant and chemosensitive
populations, providing a more personalized approach to CTC-derived xenografts, as well as patient-derived
lung cancer treatment. 74 CTCs. The findings showed that cellular subpopulations
underwent EMT after developing treatment resistance. In
4.2. Single-cell sequencing for lung cancer chemoresistant models, there was an increased expression
prognostic evaluation of signaling pathway components previously associated
with chemoresistance, such as MYC, mTOR, and Wnt.
The application of single-cell sequencing in monitoring
tumor dynamics offers unprecedented insights into The findings confirmed the presence of multiple
cancer progression and treatment response. A midkine cisplatin resistance pathways at intratumoral, intrapatient,
(MDK) is a protein that activates signaling pathways and interpatient levels. These pathways were marked by
through ligand-dependent receptor interactions, the coexistence of distinct subpopulations of cells with
resulting in specific biological responses. It is also a heterogeneous gene expression. A study found that in
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potent proangiogenic factor. Overexpression of MDK non-responsive tumors, the signaling mechanisms of
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(at both mRNA and protein levels) has been strongly T-cell receptors specific to mutated antigens (MANA)
linked to malignancy and poor prognosis. Jiang were significantly impaired. This reduction in signaling
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et al. identified two distinct subtypes using the LUAD could weaken the immune system’s ability to recognize
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scRNA-seq dataset, observing different prognostic and and destroy tumor cells, contributing to treatment
immunologic characteristics. Higher risk scores were resistance and immune evasion. In addition, these clones
associated with poorer survival outcomes and were demonstrated coordinated upregulation of checkpoint
more frequently linked to TP53 mutation, higher tumor molecules, killer suppressor receptors, and inhibitors
mutation burden values, and PD-L1 upregulation. This of T-cell activation. These observations offer valuable
model could serve as a potential biomarker for LUAD insights into resistance mechanisms that may be targeted
patients’ risk stratification and treatment response to enhance the efficacy of PD-1 blockade. He et al.
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prediction. These findings highlight the critical role analyzed the role of circadian rhythm disruption (CRD)
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of scRNA-seq in refining prognostic models for LUAD in tumors using three representative single-cell RNA-
patients and enhancing personalized therapeutic seq datasets of LUAD. The study showed that patients
approaches to improve survival outcomes. with LUAD who had high CRD scores tended to have a

Volume 9 Issue 2 (2025) 10 doi: 10.36922/ejmo.6883