Search

The 8th edition of the American Joint Commission on Cancer (AJCC) Staging System for gallbladder cancer (GBC) has been used in clinical practice, but we have found some deficiencies in this edition. Survival analyses were performed to evaluate the application of various editions of the AJCC staging systems using the Surveillance, Epidemiology, and End Results (SEER) database (N = 9616 patients) and Fudan University Zhongshan Hospital (FUZH) database (N = 327 patients). A modified staging system was proposed based on the 8th edition of the AJCC Staging System. Although all N2 diseases were grouped into stage IVB as M1 in the 8th edition, some patients with N2 diseases could undergo R0 resection, and had longer survival than patients with M1 diseases had in both cohorts (p < 0.001 in SEER, p = 0.041 in FUZH). Furthermore, in the SEER database, stage IIIA patients aberrantly had poorer survival than stage IIIB patients had (p < 0.001). Therefore, we proposed a modified staging system by rearranging the substages. N2 disease was subdivided and reappraised according to T stage, and the aberrant survival reversal of stage IIIA and stage IIIB disease was also corrected. Through our modification, the C-index of the 8th AJCC Staging System was elevated from 0.596 [95% confidence interval (CI): 0.585–0.607] to 0.623 (95% CI: 0.612–0.634) for local disease in the SEER cohort. Similar findings were also observed in the FUZH cohort. Our modified 8th AJCC Staging System is more suitable for GBC and could be adopted for clinical practice. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is a considerable challenge because of its high metastatic potential. The tumor microenvironment is characterized by nutrient starvation, which promotes tumor metastasis. Stathmin1, an important microtubuleregulating protein, is overexpressed and promotes metastasis in GBC. It remains unclear how the harsh tumor microenvironment regulates stathmin1 expression to affect GBC metastasis. We employed glucose deficiency to mimic nutrient starvation and found that glucose deficiency upregulated stathmin1 transcription. However, glucose deficiency also promoted p27 degradation. There was a significant negative correlation between stathmin1 and p27 protein levels under glucose deficiency. Further study revealed that, under glucose deficiency, human kinase interacting with stathmin (hKIS) induced phosphorylation at Ser10 of p27 and its translocation to the cytoplasm for degradation, which upregulated the transcription factor E2F1 to promote stathmin1 transcription. hKIS knockdown significantly inhibited p27 cytoplasmic translocation and its consequent degradation. Stathmin1 knockdown significantly inhibited GBC cell migration and invasion in vitro. Our study revealed the role of the hKIS/p27/E2F1 axis in upregulating stathmin1 transcription to promote GBC cell migration and invasion under glucose deficiency conditions • We model the nutrition starvation conditions with glucose deficiency; • We found increased levels of stathmin1 of GBC in nutrition starvation condition; • Glucose deficiency induced phosphorylation of p27Kip1 at Ser10 and consequently degradation; • Phosphorylation of p27 at Ser10 promoted GBC migration and invasion; • hKIS/p27/E2F1 axis regulated stathmin1 expression and GBC cell migration and invasion under glucose deficiency conditions. [ABSTRACT FROM AUTHOR]

B Introduction: b The 8 SP th sp edition of the AJCC staging system for gallbladder cancer (GBC) has been used in clinical practice, but we have found some deficiencies in the new edition. In our modified edition, N2 disease obtained a significant subdivision and reappraisal according to T stage, and the aberrant survival reversal of stage IIIA and stage IIIB was also corrected. [Extracted from the article]