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Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells.

Jeon TY, Han ME, Lee YW, Lee YS, Kim GH, Song GA, Hur GY, Kim JY, Kim HJ, Yoon S, Baek SY, Kim BS, Kim JB, Oh SO - Br. J. Cancer (2010)

Bottom Line: When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited.Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Pusan National University, Beomeo-Ri, Mulgeum-Eup, Yangsan, South Korea.

ABSTRACT

Background: Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.

Methods: Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).

Results: The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.

Conclusion: These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

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Related in: MedlinePlus

Correlationship between the stathmin1 expression level and clinicopathological characteristics. Data of stathmin-positive patients with diffuse-type gastric cancer are presented. (A) The state of stathmin1 protein expression in patients with lymph node metastasis in diffuse type gastric cancer (n=17) and in patients without metastasis (n=7). Stathmin1 protein expression in patients with lymph node metastasis is significantly higher than in patients without lymph node metastasis (*P<0.05, Mann–Whitney U-test). (B) The state of stathmin1 protein expression in patients with early stages (I and II) of diffuse type gastric cancer (n=9) and patients with advanced stages (III and IV) of diffuse-type gastric cancer (n=15). Stathmin1 protein expression in advanced stages is significantly higher than that in early stages (**P<0.01, Mann–Whitney U-test). (C) The state of stathmin1 protein expression in patients with vascular invasion in diffuse-type gastric cancer (n=14) and in patients without vascular invasion (n=10). Stathmin1 expression in patients with vascular invasion is significantly higher than in patients without vascular invasion (**P<0.01, Mann–Whitney U-test).
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fig2: Correlationship between the stathmin1 expression level and clinicopathological characteristics. Data of stathmin-positive patients with diffuse-type gastric cancer are presented. (A) The state of stathmin1 protein expression in patients with lymph node metastasis in diffuse type gastric cancer (n=17) and in patients without metastasis (n=7). Stathmin1 protein expression in patients with lymph node metastasis is significantly higher than in patients without lymph node metastasis (*P<0.05, Mann–Whitney U-test). (B) The state of stathmin1 protein expression in patients with early stages (I and II) of diffuse type gastric cancer (n=9) and patients with advanced stages (III and IV) of diffuse-type gastric cancer (n=15). Stathmin1 protein expression in advanced stages is significantly higher than that in early stages (**P<0.01, Mann–Whitney U-test). (C) The state of stathmin1 protein expression in patients with vascular invasion in diffuse-type gastric cancer (n=14) and in patients without vascular invasion (n=10). Stathmin1 expression in patients with vascular invasion is significantly higher than in patients without vascular invasion (**P<0.01, Mann–Whitney U-test).

Mentions: To characterise stathmin1 expression in human gastric cancer, we used archival paraffin-embedded tissue sections (total 226 patients) for immunohistochemistry. A rabbit anti-stathmin1 antibody (Cell Signaling Technology) was evaluated and then recommended for both western blot and immunohistochemistry by the manufacturer. To evaluate the anti-stathmin1 antibody in our lab, we performed immunohistochemistry using oral squamous cancer tissue. Stathmin1 was expressed in invading oral cancer cells (Figure 1A), which was consistent with the previous report (Kouzu et al, 2006). In normal gastric mucosa, it was difficult to detect stathmin1 expression; however, we clearly observed cytoplasmic expression of stathmin1 in gastric cancer tissue and in metastatic gastric cancer cells (Figure 1). Stathmin1 was expressed in 25.5 and 76.5% of diffuse and intestinal types of gastric cancer tissues, respectively. The correlation between the clinicopathological characteristics of patients with gastric cancer and the status of stathmin1 expression is summarised in Table 1. Interestingly, in the diffuse type of gastric cancer, stathmin1 expression was correlated with N staging (P=0.008; Table 1). The stathmin1 expression level was also significantly higher in the gastric cancer group with lymph node metastasis than in the group without lymph node metastasis (Mann–Whitney U-test, P=0.013, Figure 2). Moreover, stathmin1 expression correlated with the TNM stage grading of the diffuse type of gastric cancer (P=0.005; Table 1). The stathmin1 expression level was also significantly higher in the group with advanced gastric cancer than in the group with early-stage cancer (Mann–Whitney U-test, P=0.002, Figure 2). Furthermore, stathmin1 expression correlated with vascular invasion in diffuse-type gastric cancer (P=0.006; Table 1). The stathmin1 expression level was also significantly higher in the group with vascular invasion than in the group without vascular invasion (Mann–Whitney U-test, P=0.003, Figure 2).


Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells.

Jeon TY, Han ME, Lee YW, Lee YS, Kim GH, Song GA, Hur GY, Kim JY, Kim HJ, Yoon S, Baek SY, Kim BS, Kim JB, Oh SO - Br. J. Cancer (2010)

Correlationship between the stathmin1 expression level and clinicopathological characteristics. Data of stathmin-positive patients with diffuse-type gastric cancer are presented. (A) The state of stathmin1 protein expression in patients with lymph node metastasis in diffuse type gastric cancer (n=17) and in patients without metastasis (n=7). Stathmin1 protein expression in patients with lymph node metastasis is significantly higher than in patients without lymph node metastasis (*P<0.05, Mann–Whitney U-test). (B) The state of stathmin1 protein expression in patients with early stages (I and II) of diffuse type gastric cancer (n=9) and patients with advanced stages (III and IV) of diffuse-type gastric cancer (n=15). Stathmin1 protein expression in advanced stages is significantly higher than that in early stages (**P<0.01, Mann–Whitney U-test). (C) The state of stathmin1 protein expression in patients with vascular invasion in diffuse-type gastric cancer (n=14) and in patients without vascular invasion (n=10). Stathmin1 expression in patients with vascular invasion is significantly higher than in patients without vascular invasion (**P<0.01, Mann–Whitney U-test).
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Related In: Results  -  Collection

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fig2: Correlationship between the stathmin1 expression level and clinicopathological characteristics. Data of stathmin-positive patients with diffuse-type gastric cancer are presented. (A) The state of stathmin1 protein expression in patients with lymph node metastasis in diffuse type gastric cancer (n=17) and in patients without metastasis (n=7). Stathmin1 protein expression in patients with lymph node metastasis is significantly higher than in patients without lymph node metastasis (*P<0.05, Mann–Whitney U-test). (B) The state of stathmin1 protein expression in patients with early stages (I and II) of diffuse type gastric cancer (n=9) and patients with advanced stages (III and IV) of diffuse-type gastric cancer (n=15). Stathmin1 protein expression in advanced stages is significantly higher than that in early stages (**P<0.01, Mann–Whitney U-test). (C) The state of stathmin1 protein expression in patients with vascular invasion in diffuse-type gastric cancer (n=14) and in patients without vascular invasion (n=10). Stathmin1 expression in patients with vascular invasion is significantly higher than in patients without vascular invasion (**P<0.01, Mann–Whitney U-test).
Mentions: To characterise stathmin1 expression in human gastric cancer, we used archival paraffin-embedded tissue sections (total 226 patients) for immunohistochemistry. A rabbit anti-stathmin1 antibody (Cell Signaling Technology) was evaluated and then recommended for both western blot and immunohistochemistry by the manufacturer. To evaluate the anti-stathmin1 antibody in our lab, we performed immunohistochemistry using oral squamous cancer tissue. Stathmin1 was expressed in invading oral cancer cells (Figure 1A), which was consistent with the previous report (Kouzu et al, 2006). In normal gastric mucosa, it was difficult to detect stathmin1 expression; however, we clearly observed cytoplasmic expression of stathmin1 in gastric cancer tissue and in metastatic gastric cancer cells (Figure 1). Stathmin1 was expressed in 25.5 and 76.5% of diffuse and intestinal types of gastric cancer tissues, respectively. The correlation between the clinicopathological characteristics of patients with gastric cancer and the status of stathmin1 expression is summarised in Table 1. Interestingly, in the diffuse type of gastric cancer, stathmin1 expression was correlated with N staging (P=0.008; Table 1). The stathmin1 expression level was also significantly higher in the gastric cancer group with lymph node metastasis than in the group without lymph node metastasis (Mann–Whitney U-test, P=0.013, Figure 2). Moreover, stathmin1 expression correlated with the TNM stage grading of the diffuse type of gastric cancer (P=0.005; Table 1). The stathmin1 expression level was also significantly higher in the group with advanced gastric cancer than in the group with early-stage cancer (Mann–Whitney U-test, P=0.002, Figure 2). Furthermore, stathmin1 expression correlated with vascular invasion in diffuse-type gastric cancer (P=0.006; Table 1). The stathmin1 expression level was also significantly higher in the group with vascular invasion than in the group without vascular invasion (Mann–Whitney U-test, P=0.003, Figure 2).

Bottom Line: When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited.Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Pusan National University, Beomeo-Ri, Mulgeum-Eup, Yangsan, South Korea.

ABSTRACT

Background: Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.

Methods: Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).

Results: The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.

Conclusion: These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

Show MeSH
Related in: MedlinePlus