Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma
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ABSTRACT:
SUBMITTER: Zhang J
PROVIDER: S-EPMC10550719 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe computed tomography (CT) characteristic of ground glass opacity (GGO) were shown to be associated with clinical significance in lung adenocarcinoma. We evaluated the prognostic value of the solid component ratio of GGO IA invasive lung adenocarcinoma.MethodsWe retrospectively analyzed the records of GGO IA patients who received surgical resection from April 2012 to December 2015. The solid component ratio was calculated based on thin-slice CT scans. Baseline features were compared stratified by the ratio. Cox proportional hazard models and survival analyses were adopted to explore potential prognostic value regarding overall survival (OS) and disease-free survival (DFS).ResultsFour hundred fifteen patients were included. The higher ratio was significantly associated with larger tumor diameter, pathological subtypes and choice of surgical type. There was a significantly worse DFS with a > 50% ratio. The subgroups of 0% and ≤ 50% ratio showed close survival curves of DFS. Similar trends were observed in OS. Multivariate analyses revealed that the ratio was a significant predictor for DFS, but not for OS. No significant prognostic difference was observed between lobectomy and limited resections.ConclusionA higher solid component ratio may help to predict a significantly worse prognosis of GGO IA lung adenocarcinoma.
| S-EPMC7733294 | biostudies-literature
Project description: Not available
| S-EPMC10498257 | biostudies-literature
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.
| S-EPMC9510793 | biostudies-literature
Project description:Background The International Association for the Study of Lung Cancer (IASLC) proposed a novel grading system for invasive lung adenocarcinoma, but lymphatic invasion was not evaluated. Meanwhile, the scope of lymph node dissection in part-solid invasive lung adenocarcinoma (PSILA) is still controversial. Therefore, this study aims to explore preoperative risk factors for lymph node metastasis in PSILA, to provide reference for intraoperative dissection of lymph nodes. Methods From 2018 to 2020, clinical data of patients (stage cN0) consecutively diagnosed as PSILA were retrospectively analyzed and classified according to the novel grading system. Logistic regression was conducted to screen the clinicopathological factors of lymph node metastasis in PSILA. Results A large cohort of 960 patients with PSILA who underwent lobectomy or sub-lobectomy were enrolled. By logistic regression analyses, solid part size, bronchial cutoff sign, spiculation, and carbohydrate antigen 199 (CA199) were eventually identified as independent risk factors for lymph node metastasis, based on which a nomogram was built to preoperatively predict the risk of lymph node metastasis [area under the receiver operating characteristic curve (AUC)=0.858; concordance index = 0.857; best cutoff, 0.027]. This suggests that intraoperative systematic lymph node dissection is recommended when the predicted risk value exceeds 0.027. Reproducibility of the novel grading system was verified. Conclusions The novel IASLC grading system was applicative in real world. The nomogram for preoperative prediction of lymph node metastasis may provide reference for the lymph node dissection strategy during PSILA surgeries.
| S-EPMC9423719 | biostudies-literature
Project description:RationaleWe hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia.ObjectivePreeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies.Methods and resultsWe performed whole-genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By reverse transcriptase-polymerase chain reaction, we confirmed this finding in early-onset (<34 gestational week, n=26) and late-onset (≥34 gestational week, n=24) samples from preeclamptic women, compared with healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry, and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared with controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naive and activated macrophages lacking CD74 showed a shift toward a proinflammatory signature with an increased secretion of tumor necrosis factor-α, chemokine (C-C motif) ligand 5, and monocyte chemotactic protein-1, when cocultured with trophoblasts compared with control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFα, and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas, and impaired spiral artery remodeling with fetal growth restriction.ConclusionsCD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation toward a proinflammatory signature and a disturbed crosstalk with trophoblasts.
| S-EPMC5578411 | biostudies-literature
Project description: Not available
| S-EPMC7330336 | biostudies-literature
Project description:A total of 1039 stage I-III invasive lung adenocarcinoma including 186 solid subtype patients who have undergone radical resection were assessed for clinicopathologic characteristics, status of common driver mutations, pattern of recurrence, recurrence-free survival (RFS), overall survival (OS), post-recurrence survival (PRS) and predictive value for adjuvant chemotherapy and EGFR tyrosine kinase inhibitors (TKIs). Solid predominant adenocarcinomas were more likely to have initial distant recurrences than non-solid subtype invasive adenocarcinomas (P = 0.018). In univariate analysis, solid predominant adenocarcinoma patients had significantly worse RFS (P < 0.001), OS (P < 0.001) and PRS (P = 0.010). Multivariate analysis adjusting for clinicopathologic variables and mutational status showed that solid subtype was an independent poor prognostic factor (odds ratio = 1.876, 95% confidence interval: 1.291-3.158; P = 0.003) and an independent negative predictor for stage II-III patients undergoing adjuvant chemotherapy (odds ratio = 2.020, 95% confidence interval: 1.291-3.158; P = 0.002). In EGFR-mutated solid predominant lung adenocarcinoma patients who experienced disease recurrence, the response rate to EGFR TKIs was only 37.5%. In radically resected invasive lung adenocarcinoma, solid subtype was an independent poor prognostic factor and negative predictor for adjuvant chemotherapy.
| S-EPMC4650946 | biostudies-other
Project description:BackgroundThe accuracy of intraoperative rapid frozen pathology is suboptimal, and the assessment of invasiveness in malignant pulmonary nodules significantly influences surgical resection strategies. Predicting the invasiveness of lung adenocarcinoma based on preoperative imaging is a clinical challenge, and there are no established standards for the optimal threshold value using the threshold segmentation method to predict the invasiveness of stage T1 lung adenocarcinoma. This study aimed to explore the efficacy of three-dimensional solid component volume (3D SCV) [calculated by artificial intelligence (AI) threshold segmentation method] in predicting the aggressiveness of T1 lung adenocarcinoma and to determine its optimal threshold and cut-off point.MethodsA retrospective case-control analysis was conducted on 1,179 confirmed T1 lung adenocarcinoma nodules from two centers. AI-based threshold segmentation was used to calculate seven sets of solid component volume data (V-550, V-450, V-350, V-250, V-150, V-50, V0) at seven computed tomography (CT) threshold values (-550, -450, -350, -250, -150, -50, 0 HU). The receiver operating characteristic (ROC) curve was employed to explore the optimal threshold value for predicting the invasiveness of T1 lung adenocarcinoma based on solid component volume. Subgroup analysis was performed according to the diameter of the pulmonary nodule, divided into T1a (≤10 mm), T1b (10 mm < T1b ≤20 mm), and T1c (20 mm < T1b ≤30 mm), to investigate the optimal threshold for each subgroup.ResultsThe solid component volume was a stable predictive factor for the invasiveness of T1 lung adenocarcinoma. The optimal threshold value for predicting the invasiveness of T1 lung adenocarcinoma using AI-based 3D SCV segmentation was -350 HU, with an area under the curve (AUC) and 95% confidence interval (CI) of 0.930 (0.915-0.945), a cut-off value of 106.5 mm3, a sensitivity of 88.462%, and a specificity of 83.853%. For the T1a subgroup, the optimal threshold was -450 HU, with an AUC of 0.926, a cut-off value of 204.5 mm3, a sensitivity of 85.269%, and a specificity of 87.013%. For the T1b subgroup, the optimal threshold was -250 HU, with an AUC of 0.922, a cut-off value of 106 mm3, a sensitivity of 89.726%, and a specificity of 82.266%. For the T1c subgroup, the optimal threshold was -350 HU, with an AUC of 0.961, a cut-off value of 472 mm3, a sensitivity of 95.652%, and a specificity of 83.529%.ConclusionsThe -350 HU threshold is reasonable for predicting the invasiveness of T1 lung adenocarcinoma based on solid component volume using the threshold segmentation method. However, there are certain differences in the threshold values depending on the diameter of the pulmonary nodule.
| S-EPMC11744170 | biostudies-literature
Project description:The endoderm-lineage transcription factor FOXA2 has been shown to inhibit lung tumorigenesis in in vitro and xenograft studies using lung cancer cell lines. However, FOXA2 expression in primary lung tumors does not correlate with an improved patient survival rate, and the functional role of FOXA2 in primary lung tumors remains elusive. To understand the role of FOXA2 in primary lung tumors in vivo, here, we conditionally induced the expression of FOXA2 along with either of the two major lung cancer oncogenes, EGFRL858R or KRASG12D, in the lung epithelium of transgenic mice. Notably, FOXA2 suppressed autochthonous lung tumor development driven by EGFRL858R, whereas FOXA2 promoted tumor growth driven by KRASG12D. Importantly, FOXA2 expression along with KRASG12D produced invasive mucinous adenocarcinoma (IMA) of the lung, a fatal mucus-producing lung cancer comprising approximately 5% of human lung cancer cases. In the mouse model in vivo and human lung cancer cells in vitro, FOXA2 activated a gene regulatory network involved in the key mucous transcription factor SPDEF and upregulated MUC5AC, whose expression is critical for inducing IMA. Coexpression of FOXA2 with mutant KRAS synergistically induced MUC5AC expression compared with that induced by FOXA2 alone. ChIP-seq combined with CRISPR interference indicated that FOXA2 bound directly to the enhancer region of MUC5AC and induced the H3K27ac enhancer mark. Furthermore, FOXA2 was found to be highly expressed in primary tumors of human IMA. Collectively, this study reveals that FOXA2 is not only a biomarker but also a driver for IMA in the presence of a KRAS mutation.SignificanceFOXA2 expression combined with mutant KRAS drives invasive mucinous adenocarcinoma of the lung by synergistically promoting a mucous transcriptional program, suggesting strategies for targeting this lung cancer type that lacks effective therapies.
| S-EPMC10160002 | biostudies-literature
Project description:Preeclampsia is a disease of pregnant women, which is characterized by hypertension, proteinuria and chronic inflammation. There is a growing body of evidence that cause of preeclampsia lies within immunological aspect of pregnancy. This study aimed to analyze the role of CD74 in preeclampsia with a focus on its influence on communication between placental macrophages (Hofbauer cells) and trophoblasts. We have found CD74 to be highly dysregulated in preeclamptic placenta by real-time RT-PCR and Western blot methods. We identified Hofbauer cells to express the highest levels of CD74 in placenta by immunofluorescence and flow cytometry and that CD74 in preeclamptic Hofbauer cells is lower than in controls. We have performed a transcriptome analysis on human blood monocyte-derived macrophages that were non- or IL-4-activated and treated with small interfering RNA against CD74 (siRNA CD74) or non-targeting siRNA (siRNA non-targeting) as control.
2015-04-29 | E-MTAB-3309 | biostudies-arrayexpress