Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma

Lim, Jae‐Hak; Han, Yeon Bi; Park, Soo Young; Ahn, Soyeon; Kim, Hyojin; Kwon, Hyun Jung; Lee, Choon-Taek; Cho, Sukki; Chung, Jin-Haeng

doi:10.3390/cells10123484

Cited by 4 publications

(7 citation statements)

References 45 publications

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“…However, it is difficult to differentiate between two tumors with similar morphologies[ 6 ]. To this end, genetic analysis has recently become a widely used auxiliary diagnostic tool[ 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma: A case report

Yoshino,

Yoshida,

Yasuda

et al. 2023

World J Clin Cases

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Insulin, a small protein with 51 amino acids synthesized by pancreatic β-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma: A case report

Yoshino,

Yoshida,

Yasuda

et al. 2023

World J Clin Cases

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“…proposed that progression before tumor formation mainly follows the clonal clearance model, whereby partial clonal mutations discovered in early indeterminate lung nodules (IPNs) become clones in later IPNs, whereas inappropriate subclones are eliminated ( 29 ). Furthermore, somatic copy number alterations and allelic imbalance may occur during the transition from AAH to AIS and MIA to AIS, respectively ( 32 ) ( Figure 1 ).…”

Section: Gene Mutations In Ggnsmentioning

confidence: 99%

“…T cell types and numbers vary across pathological subtypes. A gradual decrease in CD8+ T lymphocytes, B lymphocytes, NK cells, and granulocytes occurs from normal lungs to AAH, AIS, MIA, and IAC, whereas the CD4+ T lymphocytes and CD4/CD8 ratio increase significantly under such conditions, suggesting that adaptive immune responses and immune escape begin in the preneoplastic stage ( 15 , 32 , 45 , 47 ). In addition, exhausted CD8+ T cells and Tregs increase continuously as the pathology progresses, indicating further negative immune regulation as the tumor progresses ( 47 ).…”

Section: Immune Microenvironment Characteristics Of Ggnsmentioning

confidence: 99%

“…Studies have shown that B cells in SSN exhibit inflammatory gene expression patterns, whereas B cells in advanced lung ADC are actively transcribed and have a stronger secretory phenotype ( 46 ). B cells increase gradually from normal lung tissues to ADC ( 32 ). This indicates that as the disease progresses, the number and function of B cells change further.…”

Section: Immune Microenvironment Characteristics Of Ggnsmentioning

confidence: 99%

“…Normal lung tissues and SSN have comparable percentages of NK cells; however, NK-C1 cells in SSN have a markedly higher cytotoxic proportion than in LUAD with lymph node metastasis ( 46 ). Multiple studies have revealed that NK cell activation induces a stronger immune response in GGN-ADC than in SN-ADC, and the number of NK cells decreases gradually with pathological progression, which may promote a more aggressive PNS nodule nature and immune escape ( 32 , 39 , 44 ).…”

Section: Immune Microenvironment Characteristics Of Ggnsmentioning

confidence: 99%

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Multidimensional biological characteristics of ground glass nodules

Chen,

Li,

et al. 2024

Front. Oncol.

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The detection rate of ground glass nodules (GGNs) has increased in recent years because of their malignant potential but relatively indolent biological behavior; thus, correct GGN recognition and management has become a research focus. Many scholars have explored the underlying mechanism of the indolent progression of GGNs from several perspectives, such as pathological type, genomic mutational characteristics, and immune microenvironment. GGNs have different major mutated genes at different stages of development; EGFR mutation is the most common mutation in GGNs, and p53 mutation is the most abundant mutation in the invasive stage of GGNs. Pure GGNs have fewer genomic alterations and a simpler genomic profile and exhibit a gradually evolving genomic mutation profile as the pathology progresses. Compared to advanced lung adenocarcinoma, GGN lung adenocarcinoma has a higher immune cell percentage, is under immune surveillance, and has less immune escape. However, as the pathological progression and solid component increase, negative immune regulation and immune escape increase gradually, and a suppressive immune environment is established gradually. Currently, regular computer tomography monitoring and surgery are the main treatment strategies for persistent GGNs. Stereotactic body radiotherapy and radiofrequency ablation are two local therapeutic alternatives, and systemic therapy has been progressively studied for lung cancer with GGNs. In the present review, we discuss the characterization of the multidimensional molecular evolution of GGNs that could facilitate more precise differentiation of such highly heterogeneous lesions, laying a foundation for the development of more effective individualized treatment plans.

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Multi-omics analysis unveils immunosuppressive microenvironment in the occurrence and development of multiple pulmonary lung cancers

Zhang,

Zhou,

et al. 2024

npj Precis. Onc.

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Multiple pulmonary lung cancers (MPLCs) are frequently encountered on computed tomography (CT) scanning of chest, yet their intrinsic characteristics associated with genomic features and radiological or pathological textures that may lead to distinct clinical outcomes remain largely unexplored. A total of 27 pulmonary nodules covering different radiological or pathological textures as well as matched adjacent normal tissues and blood samples were collected from patients diagnosed with MPLCs. Whole-exome sequencing (WES) and whole-transcriptome sequencing were performed. The molecular and immune features of MPLCs associated with distinct radiological or pathological textures were comprehensively investigated. Genomics analysis unveiled the distinct branches of pulmonary nodules originating independently within the same individual. EGFR and KRAS mutations were found to be prevalent in MPLCs, exhibiting mutual exclusivity. The group with KRAS mutations exhibited stronger immune signatures compared to the group with EGFR mutations. Additionally, MPLCs exhibited a pronounced immunosuppressive microenvironment, which was particularly distinct when compared with normal tissues. The expression of the FDSCP gene was specifically observed in MPLCs. When categorizing MPLCs based on radiological or pathological characteristics, a progressive increase in mutation accumulation was observed, accompanied by heightened chromatin-level instability as ground-glass opacity component declined or invasive progression occurred. A close association with the immunosuppressive microenvironment was also observed during the progression of pulmonary nodules. Notably, the upregulation of B cell and regulatory T cell marker genes occurred progressively. Immune cell abundance analysis further demonstrated a marked increase in exhausted cells and regulatory T cells during the progression of pulmonary nodules. These results were further validated by independent datasets including nCounter RNA profiling, single-cell RNA sequencing, and spatial transcriptomic datasets. Our study provided a comprehensive representation of the diverse landscape of MPLCs originating within the same individual and emphasized the significant influence of the immunosuppressive microenvironment in the occurrence and development of pulmonary nodules. These findings hold great potential for enhancing the clinical diagnosis and treatment strategies for MPLCs.

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Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma

Cited by 4 publications

References 45 publications

Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma: A case report

Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma: A case report

Multidimensional biological characteristics of ground glass nodules

Multi-omics analysis unveils immunosuppressive microenvironment in the occurrence and development of multiple pulmonary lung cancers

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