Profiling of 520 Candidate Genes in 50 Surgically Treated Chinese Small Cell Lung Cancer Patients
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Updated: Nov 1, 2025
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Published on: September 8, 2023
Ting Yuan1, Xin Wang2, Sijin Sun2
1Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Small cell lung cancer (SCLC) is one of the severe malignancies with high mortality. Surgically resected tumor tissues from 50 Chinese SCLC patients were collected for next-generation sequencing to detect 520 cancer-related genes. The most frequently altered genes were TP53 (94.0%), RB1 (86.0%), LRP1B (44.0%), SPTA1 (26.0%) and KMT2D (24.0%). We detected that NOTCH2, JAK2 and CDK12 (P<0.05) had a significantly higher mutation frequency in Chinese SCLC compared to the Cologne and MSKCC. The single nucleotide variation (SNV) is dominated by C>A (34.1%). We found a significant association between TMB-H (≥10.3muts/Mb) and ATM (P=0.023), CREBBP (P=0.010), KMT2D(P=0.050) and LRP1B (P=0.005) gene mutations in Chinese SCLC patients. Immunostaining was performed using the following antibodies: TTF-1, CgA, CD56, Syn, and Ki-67. Correlation analysis between the expression of 6 markers and mutations in signaling pathways showed that Syn and CgA expression were associated with 4 (cGMP-PKG, Chemokine, TGF-β and Phospholipase D) and 2 (cGMP-PKG and Phosphatidylinositol) signaling pathway mutations. Kaplan-Meier curve showed that age<55 years, mutant ARID2 and high TMB (≥7muts/Mb) were associated with a better prognosis, while the prognosis of patients with mutations in the Ras pathway was significantly improved. High TMB is an important prognostic factor for SCLC patients showed by multivariate analysis. In the combined cohort composed of current and two previous studies, survival analysis showed that SCLC patients with mutant LRP1B demonstrated better OS (P=0.0017). Patients with a high TMB (≥7muts/Mb) have a better prognosis (P=0.0053), consistent with our results in the Chinese cohort. We characterized the genomic alterations profile of Chinese SCLC patients and analyzed the correlation between genomic changes and immunohistochemical phenotypes at the signaling pathway level. Our data might provide useful information in the diagnosis and treatment for Chinese SCLC patients.
Insights
This study reveals key genetic alterations in Chinese small cell lung cancer (SCLC) patients, identifying TP53 and RB1 as frequently mutated. High tumor mutational burden (TMB) and specific gene mutations like LRP1B are linked to better prognoses, offering insights for SCLC treatment.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Small cell lung cancer (SCLC) is an aggressive malignancy with high mortality rates.
- Understanding the genomic landscape of SCLC is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize the genomic alterations profile in Chinese SCLC patients.
- To investigate the correlation between genomic changes, immunohistochemical phenotypes, and clinical outcomes.
Main Methods:
- Next-generation sequencing of 520 cancer-related genes in 50 Chinese SCLC patient tumor tissues.
- Immunostaining for markers including TTF-1, CgA, CD56, Syn, and Ki-67.
- Correlation analysis and survival analysis (Kaplan-Meier, multivariate) to assess prognostic factors.
Main Results:
- Frequent mutations observed in TP53 (94.0%), RB1 (86.0%), LRP1B (44.0%), SPTA1 (26.0%), and KMT2D (24.0%).
- NOTCH2, JAK2, and CDK12 mutations were significantly higher in Chinese SCLC compared to other cohorts.
- High tumor mutational burden (TMB-H) was associated with ATM, CREBBP, KMT2D, and LRP1B mutations.
- Syn and CgA expression correlated with specific signaling pathway mutations.
- Younger age (<55 years), mutant ARID2, high TMB (≥7 muts/Mb), and Ras pathway mutations were associated with better prognosis.
- Mutant LRP1B and high TMB were confirmed as favorable prognostic factors for overall survival (OS).
Conclusions:
- The study provides a comprehensive genomic profile of Chinese SCLC patients.
- Genomic alterations correlate with immunohistochemical phenotypes and clinical outcomes.
- High TMB and specific mutations like LRP1B are important prognostic indicators for SCLC, potentially guiding therapeutic strategies.
