Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer

Figure 1 Flow diagram of the study. A total of 68 cases were enrolled in the study, with explicit exclusion criteria. After collecting clinicopathological and follow-up data and conducting immunohistochemistry staining, correlations between TTK expression and clinicopathological parameters and survival prognosis were analyzed. GBC: Gallbladder cancer; PUMCH: Peking Union Medical College Hospital; TTK: Threonine and tyrosine kinase.

Figure 2 Immunohistochemical staining of tumor tissues (magnification, × 200). A-C: Cytoplasm staining with 3+, 2+ and 1+ intensity, respectively; D-F: Nuclear staining with 2+, 1+ and 0+ intensity, respectively.

Figure 3 Boxplot for H-scores in tumor and normal tissues. TTK: Threonine and tyrosine kinase.

Figure 4 Kaplan-Meier survival analyses in different subgroups, according to threonine and tyrosine kinase expression. A: The whole cohort; B: T1 + 2 group; C: T3 group; D: Negative nodal involvement group; E: Positive nodal involvement group; F: Free distant metastasis group; G: Stage I + II group; H: Stage III + IV group.TTK: Threonine and tyrosine kinase.

Figure 5 Diagram for possible mechanism concerning threonine and tyrosine kinase and carcinogenesis. A: Sister chromatids are properly arrayed in the equatorial plate at metaphase, with correct attachments to microtubules by kinetochores, attributed to the normal spindle assembly checkpoint (SAC) safeguard mechanism; B: Aberrant TTK expression, either increased or decreased expressions, could definitely compromise the functions of the SAC, with frequent chromosome missegregation errors; C: Severe chromosome missegregation errors, due to the override of SAC function, could result in chromosomal instabilities, aneuploidy formations, cell deaths and carcinogenesis; TTK: Threonine and tyrosine kinase.