Dataset Information

B7-H3 is eligible for predicting clinical outcomes in lung adenocarcinoma patients treated with EGFR tyrosine kinase inhibitors.

ABSTRACT:

Background

Not all lung adenocarcinoma (LUAD) patients with activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs) as intended. Thus, biomarkers are needed to identify patients who benefit most from EGFR-targeted therapy. Our previous in vitro data has shown that the co-signal molecule B7-H3 determines EGFR-TKI gefitinib susceptibility of EGFR-mutated LUAD cell lines, based on the potential crosslinking between B7-H3-induced signaling and EGFR signaling.

Methods

We detected tumoral B7-H3 expression in the original biopsy from 56 treatment-naïve LUAD patients and analyzed the association between high/low B7-H3 expression with the clinical outcomes of first-line anti-EGFR therapy. The main criteria for the analysis of response were overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS), and the secondary criterion was overall survival (OS).

Results

In the subgroups of B7-H3 high and low expression, the ORR were 16.0% (4/25) and 74.2% (23/31) (p<0.001), and the DCR were 36.0% (9/25) and 87.1% (27/31) (p<0.001), respectively. The PFS of B7-H3 high [median 8.7, 95% confidence interval (CI) 4.0-13.4] was significantly worse than that of B7-H3 low (median not reached) [HR 6.54 (95% CI 2.18-19.60), p=0.001]. The median OS was 15.9 (95% CI 10.0-21.8) months in the B7-H3 high cohort and 25.7 (95% CI 9.0-42.4) months in the B7-H3 low subjects [HR 2.08 (95% CI 1.07-4.02), p=0.03], respectively. Both the univariate and multivariate analyses identified B7-H3 as an independent factor associated with poor PFS (p=0.001, p=0.000) and OS (p=0.03, p=0.015).

Conclusion

B7-H3 may serve as a potential biomarker to predict clinical outcomes in EGFR-mutated LUAD patients treated with first-line EGFR-TKIs.

SUBMITTER: Yang Y

PROVIDER: S-EPMC9121599 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

B7-H3 is eligible for predicting clinical outcomes in lung adenocarcinoma patients treated with EGFR tyrosine kinase inhibitors.

Yang Ying Y Huang Jun-Feng JF Hu Bing-Qi BQ Zhou Jing J Wang Xian X Feng Zhen-Zhong ZZ Chen Yu-Ting YT Pan Fa-Ming FM Cheng Huai-Dong HD Chen Li-Wen LW

World journal of surgical oncology 20220520 1

<h4>Background</h4>Not all lung adenocarcinoma (LUAD) patients with activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs) as intended. Thus, biomarkers are needed to identify patients who benefit most from EGFR-targeted therapy. Our previous in vitro data has shown that the co-signal molecule B7-H3 determines EGFR-TKI gefitinib susceptibility of EGFR-mutated LUAD cell lines, based on the potential crosslinking between B7-H3-induced signaling an ...[more]

PMID: 35590371

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Project description:BackgroundNon-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. In Asian populations, epidermal growth factor receptor (EGFR) mutations are particularly prevalent, leading to the development of EGFR tyrosine kinase inhibitors (TKIs) to improve patient outcomes. While extensive research has been conducted on the prognosis of patients receiving EGFR-TKIs, the estimation of 5-year survival in this population remains an underexplored area.ObjectivesThis study aimed to provide real-world evidence and conduct a comprehensive analysis of the determinants influencing the 5-year survival rate in patients with EGFR-mutated NSCLC. Considering the factors identified in this study, a scoring system was developed to predict the likelihood of patients achieving this goal.DesignA retrospective cohort study utilizing a training cohort of 1,873 patients and a validation cohort of 484 patients.MethodsA logistic regression model was constructed to evaluate the weighting of factors and develop a scoring system. The Kaplan-Meier model estimated the overall survival probability, and patients were categorized into four risk groups based on their likelihood of five-year survival. The prediction performance of both the training and validation cohorts was evaluated using the area under the curve (AUC), accuracy, precision, sensitivity, specificity, and F1-score.ResultsResults indicated that age > 65 years; performance score of 2-4; metastasis to the liver, brain, bone, or pleura; and poor disease control were associated with a decreased likelihood of 5-year survival. The estimated 5-year survival rate was 23.4% (odds ratio [OR]: 20.56; 95% confidence interval [CI]: 9.06-46.64; p < 0.0001), 16.1% (OR: 12.88; 95% CI: 5.82-28.49; p < 0.0001), 7.2% (OR: 5.23; 95% CI: 2.36-11.60; p < 0.0001), and 1.5% (OR: reference) for the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively. The validation cohort further confirmed these findings, showing survival probabilities of 52.6% (OR: 96.67; 95% CI: 11.07-844.23; p < 0.0001), 21.3% (OR: 23.49; 95% CI: 3.13-176.46; p = 0.002), 14.9% (OR: 15.21; 95% CI: 2.03-114.25; p = 0.008), and 1.1% (OR: reference) for the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively. The training cohort demonstrated an AUC of 0.79 (95% CI: 0.75-0.82) and a model quality score of 0.75, indicating good predictive performance. Calibration plots demonstrated a good fit for the scoring system. For the external validation cohort, the AUC, precision, sensitivity, and specificity were 0.71, 0.74, 0.35, 0.33, respectively. The model achieved an F1-score of 0.47, reflecting adequate performance in predicting 5-year survival probabilities.ConclusionThis study identified critical prognostic factors and developed a validated scoring system for estimating 5-year survival in patients with EGFR-mutated NSCLC receiving EGFR-TKIs. While the model demonstrated robust predictive performance within the study cohort, broader applicability beyond Taiwan may require further refinements and alternative study designs.

Dataset Information

B7-H3 is eligible for predicting clinical outcomes in lung adenocarcinoma patients treated with EGFR tyrosine kinase inhibitors.

Background

Methods

Results

Conclusion

Publications

B7-H3 is eligible for predicting clinical outcomes in lung adenocarcinoma patients treated with EGFR tyrosine kinase inhibitors.

Similar Datasets

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