Differentially localized survivin and STAT3 as markers of gastric cancer progression: Association with Helicobacter pylori

Arvind Pandey, Satyendra Chandra Tripathi, Shirish Shukla, Sutapa Mahata, Kanchan Vishnoi, Sri Prakash Misra, Vatsala Misra, Sankar Mitra, Manisha Dwivedi, Alok C. Bharti

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Localization and differential expression of STAT3 and survivin in cancer cells are often related to distinct cellular functions. The involvement of survivin and STAT3 in gastric cancer has been reported in separate studies but without clear understanding of their kinetics in cancer progression. Methods: We examined intracellular distribution of STAT3 and survivin in gastric adenocarcinoma and compared it with normal and precancer tissues using immunoblotting and immunohistochemistry. Results: Analysis of a total of 156 gastric samples comprising 61 histologically normal, 30 precancerous tissues (comprising intestinal metaplasia and dysplasia), and 65 adenocarcinomas, collected as endoscopic biopsies from treatment naïve study participants, revealed a significant (P <.001) increase in overall protein levels. Survivin expression was detectable in both cytoplasmic (90.8%) and nuclear (87.7%) compartments in gastric adenocarcinomas lesions. Precancerous dysplastic gastric lesions exhibited a moderate survivin expression (56.7%) localized in cytoplasmic compartment. Similarly, STAT3 and pSTAT3 expression was detected at high level in gastric cancer lesions. The levels of compartmentalized expression of survivin and STAT3/pSTAT3 correlated in precancerous and adenocarcinoma lesions. Although overexpression of these proteins was found associated with the tobacco use and alcohol consumption, their expression invariably and strongly correlated with concurrent Helicobacter pylori infection. Receiver operating characteristic analysis of nuclear survivin, STAT3, and pSTAT3 in different study groups showed acceptable positive and negative predictive values with area under the curve above 0.8 (P <.001). Conclusion: Overall, our results suggest that overall increase in survivin and STAT3 and their subcellular localization are key determinants of gastric cancer progression, which can be collectively used as potential disease biomarkers and therapeutic targets for gastric cancer.

Original languageEnglish (US)
Article numbere1004
JournalCancer Reports
Volume1
Issue number1
DOIs
StatePublished - Jun 2018

Keywords

  • STAT3
  • dysplasia
  • gastric adenocarcinoma
  • intestinal metaplasia IV
  • survivin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Differentially localized survivin and STAT3 as markers of gastric cancer progression: Association with Helicobacter pylori'. Together they form a unique fingerprint.

Cite this