Protein expression and gene analyses of HER2, NM23, and K-RAS in gastric cancer and Helicobacter pylori-associated gastritis
Gastric cancer is ranked as the fourth most common cancer worldwide and the seventh most common cancer in the Malaysian population. Due to its vague and nonspecific symptoms, over 80% of gastric cancer cases were detected in advanced stage, leading to poor survival rate in the patients. Increa...
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| Format: | Thesis |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/71514/1/FPSK%28M%29%202012%2054%20IR.pdf http://psasir.upm.edu.my/id/eprint/71514/ |
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| Summary: | Gastric cancer is ranked as the fourth most common cancer worldwide and the seventh
most common cancer in the Malaysian population. Due to its vague and nonspecific
symptoms, over 80% of gastric cancer cases were detected in advanced stage, leading to
poor survival rate in the patients. Increasing evidence have shown that studies on the
molecular biology aspects of Helicobacter pylori-associated chronic gastritis, which is a
precursor of gastric cancer, may improve the early diagnosis of gastric cancer. To date,
the existing evidence, however, have yet to determine the specific molecular biomarkers
that may assist in the diagnosis of early gastric cancer. This preliminary study was done
to investigate the role of HER2, nm23 and K-Ras as possible molecular biomarkers in
gastric cancer and H. pylori-associated chronic gastritis. A total of 32 cases of gastric
cancer and 62 cases of H. pylori-associated chronic gastritis were analyzed using
immunohistochemical staining to investigate the protein expressions of HER2, nm23 and K-Ras. Mutational analysis on 15 cases of gastric cancer and 10 cases of H. pyloriassociated
chronic gastritis with prominent alterations in protein expressions was
performed using polymerase chain reaction and direct sequencing. Our study
demonstrated significant increase in the protein expression of nm23 in 62.5% (20/32) of
gastric cancer and 33.9% (21/62) H. pylori-associated chronic gastritis and K-Ras in
62.5% (20/32) of gastric cancer and 24.1% (15/62) of H. pylori-associated chronic
gastritis using Mann-Whitney U test (P < 0.05). The HER2 was overexpressed in 25.0%
(8/32) cases of gastric cancer. However, none of the H. pylori-associated chronic
gastritis (0.0%; 0/62) showed HER2 positivity. Using Spearmann’s rank correlation, age
was significantly correlated with the nm23 expression in H. pylori-associated chronic
gastritis (P = 0.002). Gender was significantly correlated with the K-Ras expression in
gastric cancer (P=0.026). For the mutational analysis, no mutation was detected in the
HER2 and K-Ras gene. Only one gastric cancer case (6.7%) showed a genetic variation
with a C A transition in the exon 1 of the nm23 gene. In conclusion, our findings
suggest that nm23 and K-Ras may play role as possible early biomarkers in gastric
cancers and precancerous lesions since significant increase was observed in their protein
expressions. However, the absence or low incidence of mutations may indicate that
mutations in HER2, nm23 or K-Ras gene have insignificant role in the progression of
gastric cancer. Further studies should be performed to further elucidate the role of
HER2, nm23 and K-Ras as biomarkers in gastric cancer. |
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