Fig. 7

SPINK1 is a novel circulating biomarker indicative of SASP development and predicts the adverse therapeutic outcome of cancer patients. a ELISA measurement of SPINK1 protein abundance in the serum of untreated and chemo-treated PCa patients. n = 20 per group. b ELISA assays of IL-8 protein abundance in patient serum analyzed in (a). n = 20 per group. c Scatterplot showing a correlation between SPINK1 and IL-8 in the serum of individual patients studied in (a) and (b). Pearson’s correlation coefficient, P value and confidence interval indicated. d Immunoblot of SPINK1 and IL-8 circulating in the serum of randomly selected PCa patients. Albumin, sample loading control for serum protein. n = 6 per group. e Heatmap depicting the overall correlation between stromal SPINK1, serum SPINK1, stromal IL-8, and serum IL-8 in chemo-treated patients (n = 10). The raw stromal scores derived from independent pathological reading of primary tumour tissues, while serum scores from ELISA assays. f Kaplan–Meier survival analysis of chemo-treated PCa patients. Disease-free survival (DFS) stratified according to SPINK1 expression in tumour stroma. DFS represents the length (months) of period calculated from the date of chemotherapy completion to the point of first time disease relapse. g TCGA data (Beeswarm graph) show relative expression of SPINK1 in a cohort of ovarian cancer patients (red dots) in contrast to a normal women population (black dots). h TCGA data (bar graph) show alterations of SPINK1 in human PCa patients at the genomic level, including mutation, amplification, and deep deletion. Alteration frequency is displayed in percentage. i TCGA data (bar graph) display changes of SPINK1 in human BCa patients at the genomic level with the same analysis parameters used in (h). j Illustrative diagram of SPINK1 expression in the treatment-damaged TME, pathological impact of paracrine SPINK1 on intercellular signaling network of cancer cells and its potential as a therapeutic target and novel biomarker for clinical oncology. Data of (a–e) are representative of 3 independent experiments. P values were calculated by Student’s t-test (a, b), Pearson analysis (c), and log-rank (Mantel–Cox) test (f) (***P < 0.001; ****P < 0.0001). HR hazard ratio