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.
Project description:BackgroundGround glass opacity (GGO) is associated with favorable survival in lung cancer. However, the relevant evidence of the difference in prognostic factors between GGO and pure-solid nodules for pathological stage I invasive adenocarcinoma (IAC) is limited. We aimed to identify the impact of GGO on survival and find prognostic factor for part-GGO and pure-solid patients.MethodsBetween December 2007 and August 2018, patients with pathological stage I IAC were retrospectively reviewed and categorized into the pure-GGO, part-GGO, and pure-solid groups. Survival curves were analyzed by the Kaplan-Meier method and compared by log-rank tests. Least absolute shrinkage and selection operator and Cox regression models were used to obtained prognostic factors for disease-free survival (DFS) and overall survival (OS).ResultsThe number of patients with pure-GGO, part-GGO, and pure-solid was 134, 540, and 396, respectively. Part-GGO patients with consolidation-tumor-ratio (CTR) > 0.75 had similar outcome to those with pure-solid nodules. In part-GGO patients, CTR was negatively associated with OS (P = 0.007) and solid tumor size (STS) was negatively associated with DFS (P < 0.001). Visceral pleural invasion (VPI) was negatively associated with OS (P = 0.040) and DFS (P = 0.002). Sublobectomy was negatively associated with OS (P = 0.008) and DFS (P = 0.005), while extended N1 stations examination was associated with improved DFS (P = 0.005) in pure-solid patients.ConclusionsThough GGO component is a positively prognostic factors of patients with pathological stage I IAC, a small proportion of GGO components is not associated with favorable survival. VPI, STS and CTR are the significant predictors for part-GGO patients. Sublobectomy, especially wedge resection should be used cautiously in pure-solid patients.
Project description:IntroductionThe prognosis of ground glass opacity featured lung adenocarcinomas (GGO-LUAD) is significantly better than that of solid nodule featured lung adenocarcinomas (SN-LUAD), but the specific reasons behind their indolent tumor behavior are still unclear. The purpose of this study is to investigate their differences in intratumoral microvessels, related angiogenic factors and important stromal cells.MethodsThirty patients (15 paired patients only with GGO or SN) diagnosed with pathological stage 0-I lung adenocarcinoma who underwent surgical treatment were included into this study. Immunohistochemistry was performed to stain the blood vessel markers (CD31, CD34 and CD105), LYVE-1, the cancer-associated fibroblasts (CAFs) markers (α-SMA and S100A4), TGF-β and HIF-1α from 30 patients tissue sections. At the same time, Ki67 Labeling Index (LI) extracted from pathological report of all patients was also analyzed.ResultsGGO-LUAD is more abundant than SN-LUAD in lymphatic vessel density (LVD), but similar in total microvessel density (CD31 + MVD). However, GGO-LUAD is significantly lower than SN-LUAD in CD34 + MVD and CD105 + MVD. In terms of TGF-β, HIF-1α expression and Ki67 LI level, GGO-LUAD was also significantly weaker than SN-LUAD. Moreover, the distribution of CAFs in GGO-LUAD is less than that in SN-LUAD. Regardless of the pathological type (adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) or invasive lung adenocarcinoma (IAC)), there is no difference in any of the above indicators in GGO-LUAD.ConclusionsOur finding displays that GGO-LUAD was significantly lower than SN-LUAD in CD34 + MVD and CD105 + MVD reflecting tumor angiogenesis, and the distribution of CAFs and factors related to tumor angiogenesis were also significantly lower in GGO-LUAD, which may indicate that the weak ability of angiogenesis might be the reason for the good prognosis of GGO-LUAD.
Project description:Objective Lung adenocarcinoma often includes noninvasive components with postoperative lepidic morphology on pathologic specimens that appear on preoperative high-resolution computed tomography (HRCT) images as ground-glass opacity (GGO). We aimed to disclose the role of GGO on the aggressiveness of pathologically confirmed pure invasive tumors in patients with early-stage lung adenocarcinoma. Methods The prognosis of 932 patients with clinical stage 0-IA and pathologic node-negative lung adenocarcinoma who underwent lobectomy at 3 institutions between 2010 and 2016 was investigated according to the status of GGO and lepidic components. Results The recurrence-free survival (RFS) of patients with pathologically confirmed pure invasive tumors was worse without (n = 81) than with (n = 43) GGO (69.7%; 95% confidence interval [CI], 57.3%-79.2% vs 90.5%; 95% CI, 76.6%-96.3%, P = .028). The RFS of patients with radiologically confirmed pure solid tumors was worse without (n = 81), than with (n = 173) a lepidic component (69.7%; 95% CI, 57.3%-79.2% vs 85.3%; 95% CI, 77.2%-90.7%, P = .0012). Multivariable Cox regression analysis of overall survival and RFS revealed that pure solid and pure invasive tumors, respectively, determined by HRCT and pathologic assessment together comprised an independent prognostic factor like vascular or pleural invasion for patients with early-stage lung adenocarcinoma. Conclusions Tumors of non–small cell lung cancer with pure solid and pure invasive components were more aggressive than those with some GGO and lepidic components. Complementary HRCT and pathologic findings can predict the malignant aggressiveness of adenocarcinoma. Graphical abstract Recurrence-free survival is significantly worse for patients with pure solid tumors on high-resolution computed tomography without than with lepidic components and for those with postoperative pathologic findings of pure invasive tumors without, than with ground-glass opacity components.
Project description:BackgroundIndication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas.MethodsWe retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection criterion to compare the prognosis of patients receiving lobectomy or sublobar resections.ResultsComparing to PSNs, pure GGO lesions had significantly more favorable histological characteristics and prognosis, with 100% 5-year overall survival (OS), even though 33.3% of patients with pure GGO lesions >20 mm in total lesion size received sublobar resections. For 157 pairs of PSNs with similar total lesion size but different solid component size after the first PSM, the solid-predominant subgroup had significantly worse histological characteristics and prognosis than the GGO-predominant subgroup. After the second PSM, histological characteristics and prognosis were comparable between 73 pairs of PSNs with similar solid component size but different total lesion size. Multivariable analysis showed that solid component size, rather than total lesion size or consolidation-to-tumor ratio (CTR), was an independent prognostic factor. For PSNs containing solid component size ≤2 cm, relapse-free survival (RFS) was similar after sublobar resections or lobectomy (95.0% vs. 93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9% vs. 90.0%, P=0.893).ConclusionsSolid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.
Project description:Background: Ground-glass opacity (GGO)-associated cancers are increasingly prevalent, exhibiting unique clinical and molecular features that suggest the need for a distinct treatment strategy. However, the metabolic characteristics and vulnerabilities of GGO-associated lung cancers remain unexplored. Methods: We conducted metabolomic and transcriptomic analyses on 40 pairs of GGO-associated lung cancer tissues and adjacent normal tissues. By integrating data from TCGA database and single-cell RNA sequencing, we aimed to identify aberrant metabolic pathways, establish a metabolite-associated gene signature, and pinpoint key metabolic genes. The physiological effect of key genes was detected in vitro and vivo assays. Results: We identified a 30-gene metabolite-associated signature and discovered aberrant metabolic pathways for GGO-associated lung cancer at both metabolic and transcriptional levels. Patients with this signature displayed specific prognostic and molecular features. Cox regression analysis, based on the Cancer Genome Atlas Program (TCGA) data, further narrowed down the metabolite-related gene signature, resulting in a 5-gene signature. Confirmed by single-cell RNA sequencing (GSE203360), the 5-gene signature was mainly expressed in cancer cells of GGO tissue. Real-time quantitative PCR (RT-qPCR) further validated the differential expression of these genes between GGO and adjacent normal tissue obtained from pulmonary surgery. Finally, our integrative analysis unveiled aberrant histidine metabolism at both the multi-omics and single-cell levels. Moreover, we identified MAOB as a key metabolic gene, demonstrating its ability to suppress cell proliferation, migration, and invasion in LUAD cell lines, both in vitro and in vivo. Conclusions: We identified a specific metabolite-associated gene signature and identified aberrant histidine metabolism in GGO-associated lung cancer from multiple perspectives. Notably, MAOB, a crucial component in histidine metabolism, demonstrated a significant inhibitory effect on the proliferation and metastasis of LUAD, indicating its potential significance in pathogenesis and therapeutic interventions.
Project description:BackgroundThe prognostic value of ground glass opacity (GGO) in stage IA non-small cell lung cancer (NSCLC) has been widely recognized. However, studies investigating its value in the related stage IB-IIA lung adenocarcinoma (LUAD) remains lacking. The impact of adjuvant chemotherapy (ACT) on pathological stage IB-IIA LUAD is also controversial.Materials and methodsWe retrospectively reviewed the clinical records of 501 patients with pathological stage IB-IIA LUAD at the Sun Yat-sen University Cancer Center from January 2008 to June 2018. We calculated and compared survival curves using the Kaplan-Meier test and log-rank test. Cox regression models were performed to determine independent prognostic factors of disease-free survival (DFS) and overall survival (OS). We established nomograms to predict the OS and DFS of LUAD patients. Calibration and receiver operator characteristic curves were conducted to assess the predictive performance of two nomograms. Based on the nomogram, we identified candidate patients that may most benefit from ACT after surgery.ResultsThe number of patients with pure solid, part GGO, and pure GGO nodules was 240, 242, and 19, respectively, and 125 patients who received ACT. Patients with consolidation-to-tumor ratio (CTR) <0.75 had longer OS (P = 0.026) and DFS (P = 0.003). Pathological tumor size and at least 10 lymph nodes (LNs) resection were independent prognostic factors of both OS and DFS. CTR <0.75 was positively associated with DFS. The C-index of nomograms predicting individual OS and DFS was 0.660 and 0.634, respectively. Based on the nomogram for OS, ACT was found to be a positive prognostic indicator of OS (P = 0.031, HR = 0.5141, 95% CI 0.281-0.942) in patients with nomogram total points ≥5.ConclusionCTR <0.75 is associated with a better DFS in patients with stage IB-IIA LUAD. Nomograms developed by integrating pathological tumor size, at least 10 LNs resection, and CTR ≥0.75 for predicting individual OS and DFS displayed a good predictive capacity and clinical value, which were also proved to be a useful tool for selecting patients most benefiting from ACT.