Single-cell RNA sequencing unravel distinct tumor microenvironment of different components of lung adenocarcinoma featured as mixed ground glass opacity
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ABSTRACT:
PROVIDER: PRJNA839637 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19312203_1.fastq.gz | Fastqsanger.gz | |||
| SRR19312203_2.fastq.gz | Fastqsanger.gz | |||
| SRR19312204_1.fastq.gz | Fastqsanger.gz | |||
| SRR19312204_2.fastq.gz | Fastqsanger.gz | |||
| SRR19312205_1.fastq.gz | Fastqsanger.gz |
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Project description:Single cell RNA seqencing data of six paired samples from three chinese females with early stage lung adenicarcinomas featured as mixed ground glass opacity (mGGO). Each paired samples contain one sample from solid component and one from ground-glass like component within each mGGO. The result reveiled the intratumoral heterogeneity of mGGO.
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Project description:lung cancer manifested as radiological ground-glass opacity Raw sequence reads
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Project description:Lung adenocarcinoma featured as mixed ground-glass opacity (mGGO) doubled its volume half of the time in comparison with that featured as pure ground-glass opacity (pGGO). The mechanisms underlying the heterogeneous appearance of mGGO remain elusive. In this study, we macro-dissected the solid (S) components and ground-glass (GG) components of mGGO and performed single-cell sequencing analyses of six paired components from three mGGO patients. A total of 19,391 single-cell profiles were taken into analysis, and the data of each patient were analyzed independently to obtain a common alteration. Cancer cells and macrophages were the dominant cell types in the S and GG components, respectively. Cancer cells in the S components, which showed relatively malignant phenotypes, were likely to originate from both the GG and S components and monitor the surrounding tumor microenvironment (TME) through an intricate cell interaction network. SPP1 hi macrophages were enriched in the S components and showed increased activity of chemoattraction, while macrophages in the GG components displayed an active antimicrobial process with a higher stress-induced state. In addition, the CD47-SIRPA axis was demonstrated to be critical in the maintenance of the GG components. Taken together, our study unraveled the alterations of cell components and transcriptomic features between different components in mGGOs.
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Project description:Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer death worldwide, of which approximately 85% are non-small cell lung cancer (NSCLC). The overall survival (OS) of patients with advanced NSCLC was significantly prolonged with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) axis. For early-stage lung cancer, the 5-year survival rate for patients ranges from 80% in stage IA to 41% in stage IIIA, and many cases relapse after surgical resection. Currently, multiple clinical trials have manifested the encouraging efficacy of neoadjuvant immunotherapy in stage I-IIIA resectable NSCLC. However, the effect of immunotherapy in ultra early-stage NSCLC patients with micro-invasive or even pre-invasive lesions remains unclear. In this study, we aimed to evaluate the activity and safety of sintilimab on high-risk ground glass opacity lesions in multiple primary lung cancer patients.
2024-05-01 | GSE260770 | GEO
Project description:The activity and safety of sintilimab on high-risk ground glass opacity lesions in multiple primary lung cancer patients
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Project description:BackgroundInvasive pure ground-glass opacity and pre-invasive pure ground-glass opacity have different 5-year overall survival rate and risk of lymph node metastasis and the extent of resection. It is difficult to discriminate these nodules since they share similar CT features and may occur concurrently. The objectives of this study were to investigate the feasibility of non-contrast enhanced plus contrast-enhanced computed tomography in discriminating invasive pure ground-glass opacity from pre-invasive pure ground-glass opacity.MethodsWe retrospectively examined 90 patients with pure ground-glass opacity who underwent non-contrast enhanced and contrast-enhanced CT according to a simplified protocol (one non-contrast enhanced measurement and two contrast-enhanced measurements at 30?s and 60?s after contrast injection) from 2015 to 2019. All imaging examinations were analyzed using three-dimensional computer-aided volume. Two independent samples t tests, one-way analysis of variance, chi-square test and logistic regression were used for analysis. A receiver operating characteristic curve was used to determine the optimal cut-off value of mean CT attenuation for differentiation of groups and to obtain diagnostic value.Results(1) The CT values of one non-contrast-enhanced, two contrast-enhanced and volume measurements between two groups had statistically significant differences (P <?0.001). (2) At the 30-s scan, there were more nodules in the pre-invasive group with no enhancement than in the pre-invasive group, which was statistically significant. (3) The CT value of 60-s scan was independent predictor of invasive adenocarcinoma (P =?0.019).ConclusionsNon-contrast enhanced plus two contrast-enhanced CT based on volume measurements can differentiate invasive pGGO from pre-invasive pGGO.
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Project description:BACKGROUND:Lobectomy plus lymph node dissection is the standard treatment of early-stage lung cancer, but the low lymph node metastasis rate with ground-glass opacity (GGO) makes surgeons not perform lymphadenectomy. This study aimed to re-evaluate the lymph node metastasis rate of GGO to help make a clinical judgment. METHODS:We performed this retrospective study to enroll patients who received lung cancer surgery from 2011 to 2016. Patient characteristics collected included tumor size, solid part size and lymph node metastasis rate. These patients were categorized into pure GGO and part solid GGO groups to undergo analysis. RESULTS:Lymph node metastasis rates were 0%, 3.8% and 6.9% in order of the pure GGO group, the GGO predominant group and the solid predominant group. In the lobectomy patients, the solid predominant group still showed to have the highest lymph node metastasis rate and recurrence rate (8.3% and 10.1%). CONCLUSION:It is unnecessary to perform lymphadenectomy for patients with pure GGO in view of the 0% lymph node metastasis rate. The higher lymph node metastasis rate in the patients with the solid predominant group, 6.9%, suggested that surgeons should choose a rational lymphadenectomy method according to their GGO property and clinical judgment.
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Project description:BackgroundIncreasing evidence suggests that ground-glass opacity featured lung adenocarcinoma (GGO-LUAD) and pure solid-LUAD have significantly different tumor biological behaviors; the former is usually indolent. Genetic variations fundamentally contribute to this distinct tumor behaviors. This study aims to investigate and compare the gene mutations using next-generation sequencing (NGS) technology in these two subtypes of LUAD.MethodsThe clinical data and gene testing results of 46 patients suffering from LUAD with a histologically invasive subtype ≤3 cm and operated in the Thoracic Surgery Department of Beijing Tsinghua Changgung Hospital from May 2019 to December 2022 were retrospectively analyzed; a case-control study was performed to compare the pathological and genetic differences between LUAD with a GGO component and pure solid-LUAD.ResultsNotable differences existed in vascular invasion, tumor spread through air spaces (STAS) and high-risk histological subtypes (micropapillary or solid subtypes) between the two types of LUAD with similar histologically invasive size. No significant difference was found in the mutation frequency of EGFR and KRAS. However, gene mutations were more prevalent in the cell cycle and TP53 signaling pathway for solid-LUAD. A significant difference was found in the mutation frequency of the tumor suppressor genes TP53 and CDKN2A between the two types.ConclusionsThe wild-type TP53 and CDKN2A genes could potentially be used as molecular indicators for indolent LUAD characterized by GGO-featured.
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Project description:BackgroundAlthough subcentimeter nodules represent precursor or minimally invasive lung cancer in most cases, there are still a few that are subcentimeter invasive adenocarcinoma (IAC). The aim of this study was to investigate the prognostic effect of ground-glass opacity (GGO) and the optimal surgical procedure in this special group.MethodsPatients with subcentimeter IAC were enrolled and were categorized into pure GGO, part-solid, and solid nodules based on the radiological appearance. Cox proportional hazards model and the Kaplan-Meier method were used for survival analyses.ResultsA total of 247 patients were enrolled. Among them, 66 (26.7%) were in the pure-GGO group, 107 (43.3%) were in the part-solid group, and 74 (30.0%) were in the solid group. Survival analysis demonstrated a significantly worse survival in the solid group. Cox multivariate analyses confirmed that the absence of GGO component was an independent risk factor for worse recurrence-free survival (RFS) and overall survival (OS). As for surgical procedures, lobectomy did not provide a significant better RFS or OS than sublobar resection in the whole cohort or in a subgroup of patients with solid nodules.ConclusionsThe radiological appearance stratified the prognosis of IAC with size of smaller than or equal to 1 cm. Sublobar resection may be feasible for subcentimeter IAC, even for those appearing as solid nodules; however, caution should be taken when applying wedge resection.
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Project description:As an early type of lung adenocarcinoma, ground glass nodule (GGN) has been detected increasingly and now accounts for most lung cancer outpatients. GGN has a satisfactory prognosis and its characteristics are quite different from solid adenocarcinoma (SADC). We compared the GGN adenocarcinoma (GGN-ADC) with SADC using the single-cell RNA sequencing (scRNA-seq) to fully understand GGNs. The tumor samples of five patients with lung GGN-ADCs and five with SADCs underwent surgery were digested to a single-cell suspension and analyzed using 10× Genomic scRNA-seq techniques. We obtained 60,459 cells and then classified them as eight cell types, including cancer cells, endothelial cells, fibroblasts, T cells, B cells, Nature killer cells, mast cells, and myeloid cells. We provided a comprehensive description of the cancer cells and stromal cells. We found that the signaling pathways related to cell proliferation were downregulated in GGN-ADC cancer cells, and stromal cells had different effects in GGN-ADC and SADC based on the analyses of scRNA-seq results. In GGN-ADC, the signaling pathways of angiogenesis were downregulated, fibroblasts expressed low levels of some collagens, and immune cells were more activated. Furthermore, we used flow cytometry to isolate the cancer cells and T cells in 12 GGN-ADC samples and in an equal number of SADC samples, including CD4+ T and CD8+ T cells, and validated the expression of key molecules by quantitative real-time polymerase chain reaction analyses. Through comprehensive analyses of cell phenotypes in GGNs, we provide deep insights into lung carcinogenesis that will be beneficial in lung cancer prevention and therapy.
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