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Low expression of DLC1 is predictive of poor therapeutic efficiency of fluoropyrimidine and oxaliplatin as adjuvant chemotherapy in gastric cancer.

Su Y, Lin L, Zhang J, Jiang Y, Pan C, Sun L, Duan J, Liao W - Mol Med Rep (2015)

Bottom Line: The expression of DLC1 was found to be reduced in the majority of GC samples (212/288 pairs of samples), compared with normal mucosa, in immunohistochemical analyses.Patients receiving FP‑LOHP adjuvant chemotherapy were significantly less likely to suffer GC recurrence (P=0.001) and succumb to mortality (P=0.004), compared with those who received alternative chemotherapies.In conclusion, low expression of DLC1 correlated with GC progression and is predictive of higher rates of recurrence and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

ABSTRACT
The Rho‑GTPase‑activating protein, deleted in liver cancer‑1 (DLC1), has been reported to be a tumor suppressor. However, the prognostic value of DLC1 in gastric cancer (GC) remains to be fully elucidated. Fluoropyrimidine‑oxaliplatin (FP‑LOHP) combination therapy has been widely used for the adjuvant chemotherapy of GC, however, no reliable marker has been identified to determine its efficiency. Thus, the present study performed a retrospective investigation involving 251 patients with stage IB‑III GC, who received adjuvant chemotherapy following radical resection and 37 patients with stage IV GC, who underwent palliative resection. The expression of DLC1 was found to be reduced in the majority of GC samples (212/288 pairs of samples), compared with normal mucosa, in immunohistochemical analyses. Lower expression levels of DLC1 indicated a more advanced tumor‑node‑metastasis stage, increased lymph node metastasis, deeper tumor invasion, increased tumor size and a higher rate of distant metastasis. By contrast, relatively increased expression levels of DLC1 indicated a longer time to recurrence (TTR) [hazard ratio (HR), 2.232; P=0.004] and overall survival (OS) rate (HR, 2.910; P=0.001). Patients receiving FP‑LOHP adjuvant chemotherapy were significantly less likely to suffer GC recurrence (P=0.001) and succumb to mortality (P=0.004), compared with those who received alternative chemotherapies. However, only the patients with DLC1‑positive GC receiving FP‑LOHP [DLC1 (+)/FP‑LOHP (+)] exhibited a more favorable TTR and OS, compared with the patients with DLC1 (+)/FP‑LOHP (‑) (TTR, P=0.001; OS, P=0.020). No significant improvement in clinical outcome was observed in GC patients with low DLC1 receiving FP‑LOHP treatment (TTR, P=0.270; OS, P=0.197). In conclusion, low expression of DLC1 correlated with GC progression and is predictive of higher rates of recurrence and mortality. Only patients with DLC1‑positive GC may have an improved treatment outcome from the use of FP‑LOHP as adjuvant chemotherapy.

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Expression of DLC1 is reduced in more advanced GC. Immunoreactivity scores of DLC1 were lower in GC samples with (A) later TNM stage, (B) increased lymph node metastasis, (C) increased tumor invasion, (D) larger tumor diameter and (E) increased distant metastasis. (F) No significant difference was observed among patients with GC with different degrees of differentiation. The lower and upper bars of the box plot represent the 10 and 90% percentile values. Error bars represent the 10% and 90% percentiles and dots below and above the box plots indicate values below or above the 10% and 90% percentiles, respectively. *P<0.05, #P<0.01, +P<0.001. GC, gastric cancer; DLC1, deleted in liver cancer-1; TNM, tumor-node-metastasis.
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f3-mmr-12-04-5771: Expression of DLC1 is reduced in more advanced GC. Immunoreactivity scores of DLC1 were lower in GC samples with (A) later TNM stage, (B) increased lymph node metastasis, (C) increased tumor invasion, (D) larger tumor diameter and (E) increased distant metastasis. (F) No significant difference was observed among patients with GC with different degrees of differentiation. The lower and upper bars of the box plot represent the 10 and 90% percentile values. Error bars represent the 10% and 90% percentiles and dots below and above the box plots indicate values below or above the 10% and 90% percentiles, respectively. *P<0.05, #P<0.01, +P<0.001. GC, gastric cancer; DLC1, deleted in liver cancer-1; TNM, tumor-node-metastasis.

Mentions: In order to elucidate the role of DLC1 in the progression of GC, the association between the levels of DLC1 and the clinicopathological characteristics of the patients was evaluated. Using a χ2 test, the expression level of DLC1 was be correlated with the tumor-node-metastasis (TNM) stage (P<0.001; Fig. 2A), level of lymph node metastasis (P<0.001; Fig. 2B), tumor invasion (P=0.004; Fig. 2C), tumor size (P<0.001; Fig. 2D) and distant metastasis (P=0.04; Fig. 2E). By contrast, no statistical significance was observed in the association between the expression of DLC1 and tumor differentiation status (P=0.098) (Fig. 2F), age (P=0.814; Fig. 2G) or gender (P=0.260; Fig. 2H). In addition, the overall expression level of DLC1 was observed to be significantly reduced in the GC tissues, compared with the paired normal tissues (Fig. 3A). GC tissues of a more advanced TNM stage (Fig. 3A), with increased lymph node metastasis (Fig. 3B), infiltration (Fig. 3C), tumor sizes (Fig. 3D) and distant metastasis (Fig. 3E) exhibited lower expression levels of DLC1 expression levels. However, the tumor differentiation scores were not significantly different (P=0.116; Fig. 3F). The results obtained suggested that DLC1 tended to reduce during the progression of GC. The present study subsequently investigated the association between treatment outcome and the expression of DLC1.


Low expression of DLC1 is predictive of poor therapeutic efficiency of fluoropyrimidine and oxaliplatin as adjuvant chemotherapy in gastric cancer.

Su Y, Lin L, Zhang J, Jiang Y, Pan C, Sun L, Duan J, Liao W - Mol Med Rep (2015)

Expression of DLC1 is reduced in more advanced GC. Immunoreactivity scores of DLC1 were lower in GC samples with (A) later TNM stage, (B) increased lymph node metastasis, (C) increased tumor invasion, (D) larger tumor diameter and (E) increased distant metastasis. (F) No significant difference was observed among patients with GC with different degrees of differentiation. The lower and upper bars of the box plot represent the 10 and 90% percentile values. Error bars represent the 10% and 90% percentiles and dots below and above the box plots indicate values below or above the 10% and 90% percentiles, respectively. *P<0.05, #P<0.01, +P<0.001. GC, gastric cancer; DLC1, deleted in liver cancer-1; TNM, tumor-node-metastasis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581752&req=5

f3-mmr-12-04-5771: Expression of DLC1 is reduced in more advanced GC. Immunoreactivity scores of DLC1 were lower in GC samples with (A) later TNM stage, (B) increased lymph node metastasis, (C) increased tumor invasion, (D) larger tumor diameter and (E) increased distant metastasis. (F) No significant difference was observed among patients with GC with different degrees of differentiation. The lower and upper bars of the box plot represent the 10 and 90% percentile values. Error bars represent the 10% and 90% percentiles and dots below and above the box plots indicate values below or above the 10% and 90% percentiles, respectively. *P<0.05, #P<0.01, +P<0.001. GC, gastric cancer; DLC1, deleted in liver cancer-1; TNM, tumor-node-metastasis.
Mentions: In order to elucidate the role of DLC1 in the progression of GC, the association between the levels of DLC1 and the clinicopathological characteristics of the patients was evaluated. Using a χ2 test, the expression level of DLC1 was be correlated with the tumor-node-metastasis (TNM) stage (P<0.001; Fig. 2A), level of lymph node metastasis (P<0.001; Fig. 2B), tumor invasion (P=0.004; Fig. 2C), tumor size (P<0.001; Fig. 2D) and distant metastasis (P=0.04; Fig. 2E). By contrast, no statistical significance was observed in the association between the expression of DLC1 and tumor differentiation status (P=0.098) (Fig. 2F), age (P=0.814; Fig. 2G) or gender (P=0.260; Fig. 2H). In addition, the overall expression level of DLC1 was observed to be significantly reduced in the GC tissues, compared with the paired normal tissues (Fig. 3A). GC tissues of a more advanced TNM stage (Fig. 3A), with increased lymph node metastasis (Fig. 3B), infiltration (Fig. 3C), tumor sizes (Fig. 3D) and distant metastasis (Fig. 3E) exhibited lower expression levels of DLC1 expression levels. However, the tumor differentiation scores were not significantly different (P=0.116; Fig. 3F). The results obtained suggested that DLC1 tended to reduce during the progression of GC. The present study subsequently investigated the association between treatment outcome and the expression of DLC1.

Bottom Line: The expression of DLC1 was found to be reduced in the majority of GC samples (212/288 pairs of samples), compared with normal mucosa, in immunohistochemical analyses.Patients receiving FP‑LOHP adjuvant chemotherapy were significantly less likely to suffer GC recurrence (P=0.001) and succumb to mortality (P=0.004), compared with those who received alternative chemotherapies.In conclusion, low expression of DLC1 correlated with GC progression and is predictive of higher rates of recurrence and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

ABSTRACT
The Rho‑GTPase‑activating protein, deleted in liver cancer‑1 (DLC1), has been reported to be a tumor suppressor. However, the prognostic value of DLC1 in gastric cancer (GC) remains to be fully elucidated. Fluoropyrimidine‑oxaliplatin (FP‑LOHP) combination therapy has been widely used for the adjuvant chemotherapy of GC, however, no reliable marker has been identified to determine its efficiency. Thus, the present study performed a retrospective investigation involving 251 patients with stage IB‑III GC, who received adjuvant chemotherapy following radical resection and 37 patients with stage IV GC, who underwent palliative resection. The expression of DLC1 was found to be reduced in the majority of GC samples (212/288 pairs of samples), compared with normal mucosa, in immunohistochemical analyses. Lower expression levels of DLC1 indicated a more advanced tumor‑node‑metastasis stage, increased lymph node metastasis, deeper tumor invasion, increased tumor size and a higher rate of distant metastasis. By contrast, relatively increased expression levels of DLC1 indicated a longer time to recurrence (TTR) [hazard ratio (HR), 2.232; P=0.004] and overall survival (OS) rate (HR, 2.910; P=0.001). Patients receiving FP‑LOHP adjuvant chemotherapy were significantly less likely to suffer GC recurrence (P=0.001) and succumb to mortality (P=0.004), compared with those who received alternative chemotherapies. However, only the patients with DLC1‑positive GC receiving FP‑LOHP [DLC1 (+)/FP‑LOHP (+)] exhibited a more favorable TTR and OS, compared with the patients with DLC1 (+)/FP‑LOHP (‑) (TTR, P=0.001; OS, P=0.020). No significant improvement in clinical outcome was observed in GC patients with low DLC1 receiving FP‑LOHP treatment (TTR, P=0.270; OS, P=0.197). In conclusion, low expression of DLC1 correlated with GC progression and is predictive of higher rates of recurrence and mortality. Only patients with DLC1‑positive GC may have an improved treatment outcome from the use of FP‑LOHP as adjuvant chemotherapy.

Show MeSH
Related in: MedlinePlus