Dataset Information

Relationship between stromal cells and tumor spread through air spaces in lung adenocarcinoma.

ABSTRACT:

Background

The mechanism underlying tumor spread through air spaces (STAS) has not been well studied. We investigated the role of tumor stromal cells in the pathogenesis of STAS from a pathological perspective and evaluated the prognostic significance of tumor stromal cells and STAS in postoperative patients with lung adenocarcinoma.

Methods

We retrospectively analyzed 208 postsurgical patients with stage I-IIIA lung adenocarcinoma. The presence of STAS was evaluated by hematoxylin and eosin staining. The expression of ?-smooth muscle actin (SMA)-positive cancer-associated fibroblasts (CAFs) and CD204-positive tumor-associated macrophages (TAMs) was analyzed by immunohistochemistry. A logistic regression model was applied to confirm the predictive factors of STAS. Survival analysis was performed to evaluate the effect of ?-SMA-positive CAFs, CD204-positive TAMs, and STAS on prognosis. A nomogram was generated to evaluate the prognosis of postoperative patients.

Results

Logistic regression suggested that the expression of ?-SMA-positive CAFs (P < 0.001) and the number of CD204-positive TAMs (P < 0.001) were related to the presence of STAS. The multivariate Cox proportional hazards model suggested that STAS (P = 0.004), ?-SMA-positive CAFs (P < 0.001), and CD204-positive TAMs (P < 0.001) were independent risk factors for prognosis. Harrell's c-indexes for overall and recurrence-free survival prediction based on nomograms were 0.84 (95% confidence interval 0.76-0.91) and 0.82 (95% confidence interval 0.76-0.89), respectively.

Conclusions

The presence of STAS was associated with high expression of ?-SMA and CD204 in lung adenocarcinoma. Nomograms including STAS and stromal cells as variables are recommended as practical models to evaluate the prognosis of lung adenocarcinoma patients.

SUBMITTER: Qiu X

PROVIDER: S-EPMC6360243 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Relationship between stromal cells and tumor spread through air spaces in lung adenocarcinoma.

Qiu Xie X Chen Donglai D Liu Yangyang Y Duan Shanzhou S Zhang Fuquan F Zhang Yongsheng Y Li Feng F Chen Chang C Chen Yongbing Y

Thoracic cancer 20190103 2

<h4>Background</h4>The mechanism underlying tumor spread through air spaces (STAS) has not been well studied. We investigated the role of tumor stromal cells in the pathogenesis of STAS from a pathological perspective and evaluated the prognostic significance of tumor stromal cells and STAS in postoperative patients with lung adenocarcinoma.<h4>Methods</h4>We retrospectively analyzed 208 postsurgical patients with stage I-IIIA lung adenocarcinoma. The presence of STAS was evaluated by hematoxyli ...[more]

PMID: 30605235

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Project description:BackgroundThe benefit of adjuvant chemotherapy (ACT) remains unknown for patients with stage I lung adenocarcinoma (ADC) with spread through air spaces (STAS). This study investigated the effect of adjuvant chemotherapy in stage I ADC/STAS-positive patients.MethodsA total of 3346 patients with stage I ADC from five institutions in China were identified from 2009 to 2013, of whom 1082 were diagnosed with STAS (32.3%). By using the Kaplan-Meier method and Cox proportional hazard regression model, we explored the impact of STAS on prognosis, and determined if the use of adjuvant chemotherapy was associated with improved outcomes in patients with stage I ADC/STAS-positive. A validation cohort was also included in this study.ResultsPatients with stage I ADC/STAS-positive in the primary cohort had unfavorable overall survival (OS) and disease-free survival (DFS). A multivariate Cox regression model confirmed the survival disadvantages of STAS in patients with stage I ADC [OS: hazards ratio (HR) = 1.877, 95% confidence interval (CI): 1.579-2.231; p < 0.001; DFS: HR = 1.895, 95% CI: 1.614-2.225; p < 0.001]. Lobectomy was associated with better OS and DFS than sublobar resection (SR) in both stage IA and IB ADC/STAS-positive. Similar results were observed in the validation cohort. For patients with stage IB ADC/STAS-positive, ACT was revealed as an independent factor for favorable survival (OS: HR = 0.604, 95% CI: 0.397-0.919; p = 0.018; DFS: HR = 0.565, 95% CI: 0.372-0.858; p = 0.007). However, among patients with stage IA ADC/STAS-positive, ACT was associated with improved outcomes only for those undergoing SR (OS: HR = 0.787, 95% CI: 0.359-0.949; p = 0.034; DFS: HR = 0.703, 95% CI: 0.330-0.904; p = 0.029).ConclusionThe presence of STAS was correlated with poor prognosis in patients with stage I ADC. Our study suggested that ACT might be considered for patients with stage IB ADC/STAS-positive and those with stage IA ADC/STAS-positive who underwent SR.

Project description:BackgroundThe invasive pattern called spread through air spaces (STAS) is linked to an unfavorable prognosis in patients with lung adenocarcinoma (LUAD). Using computed tomography (CT) signs alone to assess STAS is subjective and lacks quantitative evaluation, whereas spectral CT can provide quantitative analysis of tumors. The aim of this study was to investigate the association between spectral CT quantitative parameters and STAS in LUAD.MethodsWe retrospectively collected consecutive patients with LUAD who underwent surgical resection and preoperative spectral CT scan at our institution. The quantitative parameters included CT values at 40, 70, and 100 keV [CT40keVa/v, CT70keVa/v, and CT100keVa/v (a: arterial; v: venous)]; iodine concentration (ICa/ICv); normalized iodine concentration (NICa/NICv); and slope λHU of the spectral curve (λHUa/λHUv). Clinical and CT features of the patients were also collected. Statistical analysis was performed to identify the quantitative parameters, clinical and CT features that were significantly correlated with STAS status. We evaluated the diagnostic performance of significant factors or models which combined quantitative parameters and CT features, using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.ResultsWe enrolled a total of 47 patients, with 32 positive and 15 negative for STAS. The results revealed that CT100keVa (P=0.002), CT100keVv (P=0.007), pathologic stage (P=0.040), tumor density (P<0.001), spiculation (P=0.003), maximum solid component diameter (P=0.008), and the consolidation/tumor ratio (CTR) (P=0.001) were significantly correlated with STAS status. The tumor density demonstrated a superior diagnostic capability [AUC =0.824, 95% confidence interval (CI): 0.709-0.939, sensitivity =59.4%, specificity =100.0%] compared to other variables. CT100keVa exhibited the best diagnostic performance (AUC =0.779, 95% CI: 0.633-0.925, sensitivity =78.1%, specificity =80.0%) among the quantitative parameters. Combination models were then constructed by combining the quantitative parameters with CT features. The total combined model showed the highest diagnostic efficiency (AUC =0.952, 95% CI: 0.894-1.000, sensitivity =90.6%, specificity =86.7%).ConclusionsSpectral CT quantitative parameters CT100keVa and CT100keVv may be potentially useful parameters in distinguishing the STAS status in LUAD.

Project description:Background Spread through air spaces (STAS), as a new pattern of invasion, was officially proposed by the World Health Organization (WHO) in 2015, and its importance was reiterated in 2021. Since it was proposed, numerous studies have confirmed that STAS is associated with poor prognosis, but there are relatively few studies related to the prognosis of postoperative patients with lung squamous cell carcinoma. By synthesizing different predictive variables, nomogram can obtain the individual digital probability of clinical events succinctly and intuitively, which can meet our needs for personalized medicine. In this study, our goal is to explore the prognostic value of STAS in lung squamous cell carcinoma and establish a prognostic prediction model. Methods Under six inclusion criteria, 540 postoperative patients were enrolled in the study. STAS was re-evaluated by pathologists at Ningbo Clinicopathological Diagnosis Center. Progression-free survival (PFS) referred to the time from randomization to the first occurrence of disease progression or death of any cause. Recurrences were confirmed by clinical, radiological or pathological assessment. The survival information was collected by telephone and outpatient follow-up. A total of 540 patients were randomly divided into groups in a 6:4 ratio for survival analysis to determine the correlation between STAS and prognosis. Cox regression was used for univariate and multivariate analysis, so as to establish a predictive model. The assessment of the nomogram was carried out by receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA). Results The overall 5-year survival rate was 70.35% in STAS-negative patients and 42.35% in STAS-positive patients. In all cohorts, STAS-negative patients had longer 5-year PFS than STAS-positive patients (P<0.001). Multivariate analysis showed that stage [stage II P=0.008, hazard ratio (HR) =1.792; stage III P<0.001, HR =3.148], tumor differentiation (well-differentiation P=0.021, HR =0.436), and STAS (P=0.026, HR =1.470) were independent predictors of PFS. The area under the curve (AUC) of model 5 in discovery cohort is 0.720, while the AUC of model 5 in validation cohort is 0.693. Conclusions The nomogram combined with STAS can provide a personalized visual survival probability prediction map for postoperative patients with lung squamous cell carcinoma, so as to aid in the pursuit of personalized medicine to a certain extent.

Dataset Information

Relationship between stromal cells and tumor spread through air spaces in lung adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Relationship between stromal cells and tumor spread through air spaces in lung adenocarcinoma.

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