An immune checkpoint-based signature predicts prognosis and chemotherapy response for patients with small cell lung
Le Wang1, Peng Wu2, Zhibo Shen3
1Internet Medical and System Applications of National Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Background:
Therapeutic options for small cell lung cancer (SCLC), a particularly lethal malignancy, remain limited. Members of the B7-CD28 family are compelling targets for immune checkpoint blockade strategies, which involve activating, inhibiting, and fine-tuning the T cell immune response. However, their clinical features and significance have not been explored comprehensively.
Method:
We enrolled 228 patients with an initial diagnosis of SCLC, including 77 cases from Cbioportal and a validation cohort of 151 cases with qPCR data. Kaplan-Meier analysis and LASSO Cox model were used to identify a signature based on the B7-CD28 family, which was applied for accurate prediction of chemotherapy benefit and prognosis for SCLC patients. In addition, we applied bioinformatics analysis to explore potential signature-related molecular mechanisms and the immune landscape.
Results:
The mutation profiles of healthy tissues and SCLC tissues were distinct. A signature consisting of seven genes (CD86, ICOSLG, CD276, CD28, CTLA-4, PDCD1, and TMIGD2) was identified and applied to group patients based on risk level (high-risk and low-risk), producing two groups for which survival outcomes differed significantly (HR = 3.81, 95% CI: 2.16-6.74, P < 0.001). The immune checkpoint-based signature accurately predicted patient outcomes for the selected training and validation sets. Notably, low-risk patients were more likely to benefit from chemotherapy and showed greater immune activation. Additionally, time-dependent ROC curves and C-index analysis confirmed that the immune checkpoint-based signature has excellent predictive power for prognosis and chemotherapy benefit compared to clinically recognized parameters. Finally, multivariate analysis confirmed the identified signature as an independent risk factor for prognosis and chemotherapeutic response.
Conclusion:
We systematically obtained a comprehensive molecular profile for B7-CD28 family members in SCLC patients, from which we produced a reliable and robust prognostic immune checkpoint-based signature with the potential to improve prognostic stratification and therapy strategies for SCLC patients.
Insights
A new seven-gene immune checkpoint signature accurately predicts prognosis and chemotherapy benefit in small cell lung cancer (SCLC) patients. This discovery offers potential for improved risk stratification and personalized therapy strategies for SCLC.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Small cell lung cancer (SCLC) has limited therapeutic options.
- B7-CD28 family members are potential targets for immune checkpoint blockade.
- Comprehensive clinical data on these targets in SCLC is lacking.
Purpose of the Study:
- To explore the clinical features and significance of the B7-CD28 family in SCLC.
- To develop a prognostic signature for SCLC patients.
- To predict chemotherapy benefit and identify molecular mechanisms.
Main Methods:
- Utilized data from 228 SCLC patients (Cbioportal and qPCR cohorts).
- Applied Kaplan-Meier analysis and LASSO Cox model to identify a seven-gene signature (CD86, ICOSLG, CD276, CD28, CTLA-4, PDCD1, TMIGD2).
- Conducted bioinformatics analysis to explore molecular mechanisms and immune landscape.
Main Results:
- A distinct mutation profile between healthy and SCLC tissues was observed.
- The seven-gene signature stratified patients into high-risk and low-risk groups with significantly different survival outcomes (HR=3.81).
- The signature accurately predicted prognosis and chemotherapy benefit, outperforming existing parameters, with low-risk patients showing better outcomes and immune activation.
Conclusions:
- A robust prognostic immune checkpoint-based signature was developed for SCLC.
- This signature can improve prognostic stratification and guide therapy strategies.
- The findings provide a molecular profile of B7-CD28 family members in SCLC.
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