Differentially localized survivin and STAT3 as markers of gastric cancer progression: Association with Helicobacter pylori.
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.
['Pandey|Arvind|A|0000-0002-9942-5468', 'Tripathi|Satyendra Chandra|SC|', 'Shukla|Shirish|S|', 'Mahata|Sutapa|S|', 'Vishnoi|Kanchan|K|', 'Misra|Sri Prakash|SP|', 'Misra|Vatsala|V|', 'Mitra|Sankar|S|', 'Dwivedi|Manisha|M|', 'Bharti|Alok C|AC|0000-0002-5996-2832']
D000230:Adenocarcinoma D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D014408:Biomarkers, Tumor D016022:Case-Control Studies D002648:Child D018450:Disease Progression D005260:Female D005753:Gastric Mucosa D005756:Gastritis D016481:Helicobacter Infections D016480:Helicobacter pylori D006801:Humans D008297:Male D008875:Middle Aged D011230:Precancerous Conditions D012307:Risk Factors D050796:STAT3 Transcription Factor D013274:Stomach Neoplasms D000077022:Survivin D000073869:Tobacco Smoking D055815:Young Adult
survivin STAT3 gastric adenocarcinoma dysplasia intestinal metaplasia IV