Fig. 5: FGL-1 and SPINK1 are potential vulnerabilities in NSCLC-like LCNECs.
From: Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma
A Volcano plot showing differentially expressed genes between NSCLC-like (n = 89) and SCLC-like (n = 136) LCNECs in Cohort 2. Y-axis displays the −log10 p value derived from a two-sided Kolmogorov–Smirnov test. Genes with a False discovery rate of 5% and an absolute value of the log10 fold change of 0.5. B Heatmap of the top differentially expressed genes identified in (A), applicable to LCNEC and SCLC molecular subtypes. C Comparison of FGL-1 and SPINK1 log-transformed gene expression across LCNEC subtypes: NSCLC-like (n = 19), SCLC-like (n = 16), and unclassified (n = 31) LCNECs, using previously published data from George et al.11. The non-parametric two-sided Wilcoxon rank sum test was used with statistical significance defined as p < 0.05. For FGL-1, the p value for NSCLC-like versus SCLC-like LCNEC was 8.4 × 10−6; for NSCLC-like versus unclassified LCNEC, 0.0003; and for unclassified versus SCLC-like LCNEC, 0.01. For SPINK1, the p value for NSCLC-like versus SCLC-like LCNEC was 1 × 10−6; for NSCLC-like versus unclassified LCNEC, 8.3 × 10−5; and for unclassified versus SCLC-like LCNEC, 0.003. D Comparison of relative FGL-1 protein expression across 54 cell lines from various cancer types, using data from the DepMap dataset. E Box-and-whisker plots comparing median FGL-1 expression across 20 cancer types from Caris Life Sciences (n = 125,632 tumor samples). Dashed lines from top to bottom represent median FGL-1 expression in NSCLC-like, all, and SCLC-like LCNECs, respectively. For the box-and-whisker plots, the center line indicates the median, the bounds of the box represent the 25th and 75th percentiles (interquartile range), and the whiskers extend to the minimum and maximum values. Each point represents an individual patient tumor (biological replicate). F GSEA plots showing pathways enriched in FGL-1 high versus FGL-1 low NSCLC-like LCNECs. G Representative immunofluorescence staining of FGL-1 (green) and DAPI (white) in 2 NSCLC-like LCNECs, 1 SCLC-like LCNEC, 3 NSCLC, and 4 SCLC (H). 20× magnification is shown. The experiment was repeated using independent biological replicates (no technical replicates). Dot plot comparing tumor-infiltrating lymphocyte (TIL) counts among patients with lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), small cell lung cancer (SCLC), and large cell neuroendocrine carcinoma (LCNEC). Median values are shown per group. The non-parametric two-sided Wilcoxon rank sum test was used with statistical significance defined as p < 0.05. TIL tumor-infiltrating lymphocytes, LUSC lung squamous cell carcinoma, LUAD lung adenocarcinoma, NSCLC non-small cell lung cancer, SCLC small cell lung cancer, LCNEC large cell neuroendocrine carcinoma. The p value for SCLC versus NSCLC-like LCNEC was 0.005; for LUAD versus NSCLC-like LCNEC, 0.009; and for LUSC versus NSCLC-like LCNEC, 0.006.
