Dataset Information

Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer.

ABSTRACT:

Purpose

To improve the understanding of special types of tumors, we summarized and analyzed the clinicopathological features and prognostic factors of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC).

Methods

We selected 105 patients with SMARCA4-dNSCLC and 221 patients with SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) by performing immunohistochemical analysis of 1520 NSCLC samples, and we assessed the patients' clinicopathological features and survival state.

Results

(1) SMARCA4-dNSCLC was significantly associated with older age, male sex, smoking history, larger invasive tumor size, higher tumor proliferation index (Ki-67), more adrenal metastases, more lymph node metastases, and few EGFR mutations (p < 0.05). The tumors were mostly negative for thyroid transcription factor-1 (TTF-1), CD34, and p40 and positive for cytokeratin 7 (CK7) in immunohistochemistry (IHC). Nineteen SMARCA4-dNSCLC patients mostly had TP53, SMARCA4, and LRP1B mutations, and 48% of them had SMARCA4 frameshift mutations. SMARCA4-dNSCLC patients have a worse prognosis than SMARCA4-iNSCLC patients (HR: 0.27; 95% CI: 0.17-0.45). The overall survival (OS) of patients with stage III SMARCA4-dNSCLC was worse than that of patients with SMARCA4-iNSCLC, and the OS of stage IV SMARCA4-dNSCLC patients was also worse than that of SMARCA4-iNSCLC patients (p < 0.01). (2) Multivariate regression analysis showed that sex (HR: 4.12; 95% CI: 1.03-16.39) and smoking history (HR: 2.29; 95% CI: 1.04-5.02) had significant effects on the survival time of SMARCA4-dNSCLC patients. In SMARCA4-dNSCLC patients without distant metastases (stage I-III), patients with stage N2 or N3 lymph node metastases (HR: 6.35; 95% CI: 1.07-37.47) had a poor prognosis. Among patients with SMARCA4-dNSCLC who were treated and had distant metastases (stage IV), male patients and patients treated with immunotherapy combined with chemotherapy showed a longer median overall survival (mOS).

Conclusion

SMARCA4-dNSCLC has unique clinicopathological features and a shorter survival prognosis than SMARCA4-iNSCLC. The efficacy of immunotherapy combined with chemotherapy needs to be observed for longer periods.

SUBMITTER: Liang X

PROVIDER: S-EPMC10358186 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer.

Liang Xiyue X Gao Xianzheng X Wang Feng F Li Shenglei S Zhou Yashu Y Guo Peng P Meng Yuanyuan Y Lu Taiying T

Cancer medicine 20230515 13

<h4>Purpose</h4>To improve the understanding of special types of tumors, we summarized and analyzed the clinicopathological features and prognostic factors of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC).<h4>Methods</h4>We selected 105 patients with SMARCA4-dNSCLC and 221 patients with SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) by performing immunohistochemical analysis of 1520 NSCLC samples, and we assessed the patients' clinicopathological features and survival ...[more]

PMID: 37184108

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Project description:BackgroundThoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a distinct clinicopathological entity with an aggressive clinical course. Additionally, SMARCA4/BRG1 deficiency can be observed in a few patients with non-small cell lung cancer (NSCLC). We aimed to compare the clinicopathological, immunohistochemical and prognostic features of SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) with those of thoracic SMARCA4-UT.MethodsPatients with BRG1-deficient tumors in the lung or thorax were enrolled in the study from the Department of Pathology of West China Hospital, Sichuan University, from January 2014 to June 2022. We retrospectively collected the clinicopathological and immunohistochemical features and outcomes of these patients.ResultsSeventy-two patients had tumors in the lung or thorax with BRG1-deficient expression, including 52 patients with SMARCA4-dNSCLC and 20 patients with thoracic SMARCA4-UT. Among the patients with SMARCA4-dNSCLC, 98.1% were male, 85.7% were smokers, and 79.5% (35/44) had tumor-node-metas-tasis (TNM) III-IV tumors. Among the patients with thoracic SMARCA4-UT, all were males who smoked, and 93.75% (15/16) had TNM III-IV tumors. Pure solid architecture and necrosis were the predominant pathological features. Rhabdoid morphology was observed in some SMARCA4-dNSCLCs (10/52, 19.2%) and thoracic SMARCA4-UTs (11/20, 55%). In most patients with thoracic SMARCA4-UT, the tumors exhibited scattered weak expression or negative expression of epithelial markers, and positive expression of CD34 and Syn. Overall survival (OS) and progression-free survival (PFS) were not significantly different between patients with SMARCA4-dNSCLC and patients with thoracic SMARCA4-UT (p = 0.63 and p = 0.20, respectively).ConclusionsThoracic SMARCA4-DTs include SMARCA4-dNSCLC and thoracic SMARCA4-UT. Both have overlapping clinicopathological features and poor prognosis. We hypothesize that thoracic SMARCA4-UT may be the undifferentiated or dedifferentiated form of SMARCA4-dNSCLC. However, further studies with larger cohorts and longer follow-up periods are needed.

Project description:BackgroundPatients with non-small cell lung cancer (NSCLC) carrying SMARCA4 mutations (SMARCA4-Mut) tend to have more advanced disease and a poor prognosis. However, due to the rarity of this mutation and the lack of related studies, the characteristics of SMARCA4-Mut NSCLC patients remains poorly determined. To clarify the clinical characteristics and prognostic factors of SMARCA4-Mut NSCLC, we initiated the present study to provide a clinical reference.MethodsWe used data from two cohorts of NSCLC-SMARCA4-mutated samples: The Cancer Genome Atlas (TCGA) database and our center's clinical data. The TCGA database was used to obtain 481 NSCLC-SMARCA4-Mut samples for clinical characterization. The center collected data on 224 consecutive NSCLC patients treated between December 2020 to July 2022. Among them, 26 harbored SMARCA4 mutations, and 20 were eligible for inclusion in the study. Clinical, pathological, and molecular features, as well as prognostic role of SMARCA4 mutations were analyzed. Additionally, we analyzed the prognostic impact of Napsin A expression in SMARCA4-Mut patients.ResultsThe TCGA database included 480 patients with SMARCA4-Mut NSCLC, 311 males (64.8%) and 169 females (35.2%), with a median age of 67 years. Among the 20 SMARCA4-Mut patients in our center series, 12 (60%) were males and 8 (40%) females, with a median age of 63. The intergroup prognostic correlation analysis showed that SMARCA4-Mut patients had significantly worse prognosis than those the wild-type SMARCA4 (SMARCA4-WT) (P=0.04). Within the SMARCA4-Mut group, patients with Napsin A expression had longer overall survival (OS) (P=0.03) than those without expression. Median survival in the Napsin A-positive and negative groups was 32 and 15 months, respectively. According to time-dependent receiver operating curve analysis, patients with Napsin A expression had significantly longer first-line treatment progression-free survival (PFS1) [area under the curve (AUC) =0.748] and OS (AUC =0.586). No prognostic value of Napsin A was found in patients SMARCA4-WT patients.ConclusionsSMARCA4-Mut is an adverse prognostic feature in NSCLC patients. Napsin A expression in SMARCA4-Mut patients is associated with prolonged OS.

Project description:BackgroundSMARCA4/BRG1-deficient non-small cell lung cancer (S/B-d NSCLC) is a rare subtype of non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical, imaging, serum tumor marker, and pathological features of S/B-d NSCLC, particularly computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan features.MethodsOur analysis included 23 patients with pathologically confirmed S/B-d NSCLC from January 2021 to December 2023. A retrospective analysis of clinical, serum tumor markers, imaging [including CT, FDG PET/CT, magnetic resonance imaging (MRI)], pathological features, treatment protocols, and follow-up results was performed. Independent samples t-tests were used to assess statistical differences in short diameters and maximum standardized uptake value (SUVmax) between groups.ResultsS/B-d NSCLC occurs predominantly in male patients with a history of smoking and a mean age of 62.78 years (39-77 years). S/B-d NSCLC was found incidentally during physical examination in 56.52% of patients. The CT scan features were as follows: predominantly tumors (72.73%), peripheral in the lungs (77.27%), round or roundish morphology (81.28%), pleural or vascular invasion (95.46%), and moderately to severely enhanced (59.09%). The FDG PET/CT showed FDG-avid with mean SUVmax of 14.78±9.57. Lung cancer-related serum tumor markers had high positivity rates for carcinoembryonic antigen (CEA) (66.67%), recombinant cytokeratin fragment antigen 21-1 (CYFRA21-1) (61.91%), and carbohydrate antigen 125 (CA125) (57.14%). Pathological features are often characterized by grading (poor differentiation, 100%), tumor spread through the air space (STAS, 85.71%), and vascular invasion (85.71%). Immunohistochemistry showed that SMARCA4 (BRG1) was absent, and P40, P63, ALK-Ventana ALK (D5F3), and p-TRK were often negative. Genetic tests showed that the positivity rate of TP53 (76.92%) and KEAP1 (53.85%) was high. Despite diverse treatment options being available, high rates of progression during treatment and poor prognosis were observed. Among CT features (N=22), the short diameter of CT-diagnosed metastatic lymph nodes (LNs) was larger than that of non-metastatic LNs, and the difference was statistically significant (P=0.02). Among the FDG PET/CT features (N=12), SUVmax was larger in tumor group than lesion group, SUVmax was larger in M1 group than M0 group, and the difference was statistically significant in both groups (P=0.001 and P=0.04).ConclusionsS/B-d NSCLC has distinct features in epidemiology, serum tumor markers, imaging, and pathology. In particular, FDG-avid is evident in the FDG PET/CT scan. The size of the lesion and the degree of FDG avidity provide information about the degree of malignancy and the high probability of distant metastasis in S/B-d NSCLC. FDG PET/CT is recommended when S/B-d NSCLC is suspected based on CT features, especially for large lesions. The FDG PET/CT scan can help with accurate staging and individual treatment planning.

Project description:IntroductionCancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients.MethodsSeventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine differences in survival.ResultsCompared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049).ConclusionWe profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

Dataset Information

Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer.

Purpose

Methods

Results

Conclusion

Publications

Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer.

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