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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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DLC1-negative patients are more likely to exhibit GC recurrence and shorter survival rates. Kaplan-Meier analysis was performed in (A) patients with stage IB-III GC for time to recurrence and in (B) patients with stage IB-IV GC for OS. Stratified analysis was also performed to evaluate the effect of DLC1 on OS in patients who (C) received radical resection (stage IB-III) and (D) underwent palliative surgery (stage IV). DLC1, deleted in liver cancer-1; GC, gastric cancer; OS, overall survival rate.
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f4-mmr-12-04-5771: DLC1-negative patients are more likely to exhibit GC recurrence and shorter survival rates. Kaplan-Meier analysis was performed in (A) patients with stage IB-III GC for time to recurrence and in (B) patients with stage IB-IV GC for OS. Stratified analysis was also performed to evaluate the effect of DLC1 on OS in patients who (C) received radical resection (stage IB-III) and (D) underwent palliative surgery (stage IV). DLC1, deleted in liver cancer-1; GC, gastric cancer; OS, overall survival rate.

Mentions: To further examine the effect of negative expression of DLC1 on GC recurrence and mortality rates, TTR and OS were evaluated using Kaplan-Meier survival analysis. In the 251 patients with stage IB-III GC, TTR was significantly shorter in patients with DLC1-negative GC, compared with those with DLC1-positive GC (estimated 3-year recurrence-free survival rates, 30.1, vs. 73.4%, respectively; Fig. 4A). In addition, in the 288 patients with stage IB-IV, those with DLC1-negative GC demonstrated significantly shorter OS rates, compared with those with DLC1-positive GC (estimated 5-year OS rate, 21.2, vs. 62.8%; Fig. 4B). Stratified analysis was also performed to evaluate the effect of DLC1 on OS in patients with stage IB-III GC, who received radical resection and those with stage IV GC, who underwent palliative surgery. DLC1 deficiency was indicative of reduced survival rates in patients with stage IB-III (Fig. 4C) and stage IV (Fig. 4D). Among the patients with DLC1-negative GC, the median TTR in those with stage IB-III GC was 26.0 months and the median OS in the patients with stage IB-IV GC was 36.0 months. However, more than half of the patients with DLC1-positive stage IB-III cancer remained relapse-free at the end of the follow-up.


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)

DLC1-negative patients are more likely to exhibit GC recurrence and shorter survival rates. Kaplan-Meier analysis was performed in (A) patients with stage IB-III GC for time to recurrence and in (B) patients with stage IB-IV GC for OS. Stratified analysis was also performed to evaluate the effect of DLC1 on OS in patients who (C) received radical resection (stage IB-III) and (D) underwent palliative surgery (stage IV). DLC1, deleted in liver cancer-1; GC, gastric cancer; OS, overall survival rate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-12-04-5771: DLC1-negative patients are more likely to exhibit GC recurrence and shorter survival rates. Kaplan-Meier analysis was performed in (A) patients with stage IB-III GC for time to recurrence and in (B) patients with stage IB-IV GC for OS. Stratified analysis was also performed to evaluate the effect of DLC1 on OS in patients who (C) received radical resection (stage IB-III) and (D) underwent palliative surgery (stage IV). DLC1, deleted in liver cancer-1; GC, gastric cancer; OS, overall survival rate.
Mentions: To further examine the effect of negative expression of DLC1 on GC recurrence and mortality rates, TTR and OS were evaluated using Kaplan-Meier survival analysis. In the 251 patients with stage IB-III GC, TTR was significantly shorter in patients with DLC1-negative GC, compared with those with DLC1-positive GC (estimated 3-year recurrence-free survival rates, 30.1, vs. 73.4%, respectively; Fig. 4A). In addition, in the 288 patients with stage IB-IV, those with DLC1-negative GC demonstrated significantly shorter OS rates, compared with those with DLC1-positive GC (estimated 5-year OS rate, 21.2, vs. 62.8%; Fig. 4B). Stratified analysis was also performed to evaluate the effect of DLC1 on OS in patients with stage IB-III GC, who received radical resection and those with stage IV GC, who underwent palliative surgery. DLC1 deficiency was indicative of reduced survival rates in patients with stage IB-III (Fig. 4C) and stage IV (Fig. 4D). Among the patients with DLC1-negative GC, the median TTR in those with stage IB-III GC was 26.0 months and the median OS in the patients with stage IB-IV GC was 36.0 months. However, more than half of the patients with DLC1-positive stage IB-III cancer remained relapse-free at the end of the follow-up.

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