Dataset Information

Genomic landscape of ground glass opacities (GGOs) in East Asians.

ABSTRACT:

Background

Understanding the genomic landscape of early-stage lung adenocarcinoma (LUAD) may provide new insights into the molecular evolution in the early stages of LUAD.

Methods

Through sequencing of 79 spatially distinct regions from 37 patients with ground glass opacities (GGOs), we provided a comprehensive mutational landscape of GGOs, highlighting the importance of ancestry differences.

Results

Our study had several interesting features. First, epidermal growth factor receptor (EGFR), BRAF (v-RAF murine sarcoma viral oncogene homologue B1), and ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2, also known as HER2) were more frequently mutated in our study, which supports the notion that EGFR is considered to be a major driver and tends to drive the occurrence of LUAD. Second, Signature 1, Signature 3, and Signature 6 were identified in patients with GGOs. Our results further suggested that Signature 1 was more prominent among early mutations. Third, compared with LUADs, GGOs exhibited significantly lower levers of arm-level copy number variation (CNV)-which alter the diploid status of DNA, and lower focal CNVs.

Conclusions

In our study, 79 samples of patients were included to analyze the GGO gene profile, revealing the genetic heterogeneity of GGO in East Asian population, and providing guidance for prognosis analysis of GGO patients by comparison with LUAD. Our study revealed that GGOs had fewer genomic alterations and simpler genomic profiles than LUADs. The most commonly altered processes were related to the receptor tyrosine kinase (RTK)/Ras/phosphatidylinositol-3-kinase (PI3K) signaling pathways in GGOs, and EGFR alterations were the dominant genetic changes across all targetable somatic changes.

SUBMITTER: Cao P

PROVIDER: S-EPMC8107556 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Genomic landscape of ground glass opacities (GGOs) in East Asians.

Cao Peng P Hu Shan S Kong Kangle K Han Peng P Yue Jiaqi J Deng Yu Y Zhao Bo B Li Fan F

Journal of thoracic disease 20210401 4

<h4>Background</h4>Understanding the genomic landscape of early-stage lung adenocarcinoma (LUAD) may provide new insights into the molecular evolution in the early stages of LUAD.<h4>Methods</h4>Through sequencing of 79 spatially distinct regions from 37 patients with ground glass opacities (GGOs), we provided a comprehensive mutational landscape of GGOs, highlighting the importance of ancestry differences.<h4>Results</h4>Our study had several interesting features. First, epidermal growth factor ...[more]

PMID: 34012587

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Project description:PURPOSE:Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. METHODS:In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging. RESULTS:We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. CONCLUSIONS:This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.

Project description:Objective: Pure ground-glass opacity (GGO) nodules have been detected with increasing frequency using computed tomography (CT). We performed a retrospective study to clarify whether lung cancer patient prognoses correlated with pure GGO nodules. We also analyzed the clinical characters of patients with pure GGO nodules to provide diagnostic guidance on lung cancer identification and treatment of patients in clinical practice. Methods: We enrolled 39 of 1422 patients with pure GGO nodules who accepted surgical treatment of the lung cancer nodules, and reviewed materials from 404 patients to verify our conclusions. To discover which factors were prognostically significant, we used the Kaplan-Meier method to estimate the overall survival (OS) and progression-free survival (PFS) curves. Age, gender, smoking history, histology, tumor size, and stage were the factors examined in our study. We also performed subgroup and matching group analyses to clarify the correlation between the presence of pure GGO nodules and prognoses. Results: Pure GGO nodules were associated with non-smoking females that had adenocarcinoma. The prognoses of patients in the pure GGO nodule group was better than those in the non-pure GGO nodule group (p = 0.046). Age, grade, and stage (including tumor size and lymph node metastases) were had prognostic significance. In the matching group stage assessments, although patient prognoses were not significantly different among patients of the GGO group compared with thoses of the other group in long-term, while in the short term, patients with pure GGO nodules had longer PFS. Non-smoking female patients with lung cancer were more likely to have adenocarcinoma. Conclusions: As a subgroup of GGO nodules, pure GGO nodules predict a better prognosis in all lung cancer patients. Wheras our study showed that lung patients with pure GGO nodules in similar stages were not significantly different in long-term prognoses, in the short term; patients with pure GGO nodules had longer PFS.

Project description:BackgroundBilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy.MethodsA total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers.ResultsGrade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs.ConclusionOur study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.

Project description:BACKGROUND:There is an increasing incidence rate of ground-glass opacity (GGO), especially for multiple GGOs (?2). Whether it is safe and feasible to have bilateral simultaneous surgical resection remains unknown. The purpose of this study is to summarize the experience of surgical resection of patients with multiple GGOs in our Hospital in recent years, and to discuss the above questions. METHODS:Clinical datas of patients who underwent one-stage bilateral uni-portal VATS resections of multiple pulmonary ground glass opacities and had routine pathological examination were collected from May 2016 to May 2019 in our hospital. RESULTS:A total of 34 patients underwent simultaneous bilateral surgical resection of multiple GGO lesions, 28 were women,6 were men, the average age of total patients was 57.9?±?6.7?years. All patients underwent bilateral uni-portal video-assisted thoracoscopic surgery (Uni-portal VATS), the average intraoperative blood loss was 100.9?±?67.7?ml, the average operation time was 140?± 74.8?min, the average thoracic drainage time was 2.8?±?3.1?days, and the average postoperative hospital stay was 4.2?±?4.3?days. Postoperative complications including: 2 cases of infection, 3 cases of atrial fibrillation, and 5 cases of persistent air leakage for more than 3?days. All of them improved after treatment, and there were no serious complications and deaths in perioperative period. A total of 76 GGO lesions were resected, with a total malignancy rate of 81.6%, including 40 were pure GGO, of which 28 were malignant (70%), and the average diameter of them were 9.6?±?3.8?mm; 36 were mixed GGO, of which 34 were malignant (94.4%), the average diameter of them were 15.6?±?6.6?mm.Mean postoperative follow-up was 28.4 (range, 3-39) months. There was neither recurrence nor deaths at final follow-up. CONCLUSION:The malignancy rate of multiple GGOs is high. Therefore, when the lung function is allowed,one-stage bilateral uni-portal VATS can be considered. According to experience of main surgeon and the frozen biopsy, either sub-lobar resection or lobectomy was acceptable. The risk of postoperative complications and the prognosis were optimal.

Dataset Information

Genomic landscape of ground glass opacities (GGOs) in East Asians.

Background

Methods

Results

Conclusions

Publications

Genomic landscape of ground glass opacities (GGOs) in East Asians.

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