Fig. 6: JAK2-induced BECN1 Y333 phosphorylation is a predictive marker for poor cancer prognosis and chemotherapy resistance.

a Representative results of immunohistochemical staining for p-JAK2 and p-BECN1 (Y333) in the same tumor tissues from 65 clinical CRC patients. Scale bars, 20 μm. b Statistical analysis of the expression of p-JAK2 and p-BECN1 (Y333) in tumor tissues. ***P < 0.001. The values are presented as the means ± s.d.; the p value (χ²-Test) is shown. c Representative results of immunohistochemical staining for p-BECN1 (Y333) in tumor tissues and adjacent normal tissues. Scale bars, 200 μm (top) and 50 μm (bottom). d Statistical analysis of p-BECN1 (Y333) levels in tumor tissues and adjacent normal tissues. ***P < 0.001. Data are presented as the means ± s.d., and the p value was determined by unpaired Student’s t test. e Overall survival was compared between CRC patients with low and high levels of p-BECN1 (Y333) (n = 44 low p-BECN1 (Y333) levels; n = 57 high p-BECN1 (Y333) levels). Survival data were analyzed by the Kaplan–Meier method and log-rank test. f, g Univariate analysis (f) and multivariate analysis (g) were performed in Cohort 2. The bars correspond to 95% confidence intervals. h, i Synergy analysis of the JAK2 inhibitor CHZ868 and chemotherapy drugs (5-Fu or OXA) in LoVo cells. Cells were treated with the indicated concentrations of CHZ868 and 5-Fu (h) or OXA (i) for 36 h. The combination index (CI) value was examined. The CI value indicates the following: >1.15, synergism = 0.85–1.15, additive effect; and <0.85, antagonism. j Proposed schematic diagram of IL-6-mediated autophagy activation to promote chemotherapy resistance in colorectal cancer. Source data are provided in the Source Data file.