Fig. 2: sGCs are upregulated during disease progression and correlate with acquired rather than inherent chemoresistance in SCLC. | Nature Communications

Fig. 2: sGCs are upregulated during disease progression and correlate with acquired rather than inherent chemoresistance in SCLC.

From: Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer

Fig. 2

a RNA-seq of six CDX progression models showing recurrent differentially expressed genes. Volcano plot indicates recurrent significantly (padj < 0.05) upregulated (log2FC > 1) and downregulated (log2FC < −1) genes in six progression models vs. corresponding pre-treatment models. Genes that passed only one of these thresholds are indicated in blue/green, p values from negative binomial distribution, calculated by DESeq2. b IHC of paired CDX tumours for GUCY1B1 expression (brown stain). Scale bar set to 50 μm and equivalent throughout panels. Whole tumours were analysed and representative areas are shown. Representative images from one mouse per group are shown. c Western blot for GUCY1B1 expression in paired CDX progression tumour lysates. Blotting was performed on three animals per model (n = 3, Supplementary Fig. 2e) and a representative western blot is shown. d Correlation of change in GUCY1B1 protein expression and change tumour volume in progression and baseline CDX models after treatment with cisplatin/etoposide. p = 0.137, Pearson R2 value = 0.462, from linear regression. e Comparison of donor patients’ chemotherapy responses with GUCY1B1 expression (variance-stabilizing transformation, VST) of the corresponding CDX model determined by RNA-seq. f Comparison of GUCY1B1 TMA % positive tumour and stage of disease of treatment-naive patients. n = 37 limited and n = 7 extensive stage patients, data are represented as mean ± 95% confidence interval (CI). P values from two-sided unpaired Student’s t-test, t = 1.570, d.f. = 42. g Comparison of GUCY1B1 % positive tumour and response of treatment-naive patients. Response summarizes partial and complete response; no response stable and progressive disease. n = 26 response group and n = 8 no response group, data are represented as mean ± 95% CI. P values from two-sided unpaired Student’s t-test, t = 0.573, d.f. = 32. h Survival analysis of treatment-naive SCLC patients using dichotomized % positive tumour. Two-sided Kaplan–Meier (log rank) analysis was performed to estimate the median survival in each group. Wald test = 0.85, log-rank chi square value = 0.62, d.f. = 1, and p value = 0.438. See also Supplementary Fig. 2.

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