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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 is frequently deficient in GC. (A) Negative expression of DLC1 was more frequently observed in GC samples, compared with the matched para-cancerous normal tissues (P<0.001), particularly in GC with increased (A) TNM stage (P<0.001), (B) lymph node metastasis (P<0.001), (C) invasion (P=0.004), (D) tumor diameter (P<0.001) and (E) distant metastasis (P=0.040). The expression of DLC1 was not significantly associated with (F) tumor differentiation (P=0.098), (G) age (P=0.814) or (H) gender (P=0.260). DLC1, deleted in liver cancer-1; GC, gastric cancer; TNM, tumor-node-metastasis.
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f2-mmr-12-04-5771: DLC1 is frequently deficient in GC. (A) Negative expression of DLC1 was more frequently observed in GC samples, compared with the matched para-cancerous normal tissues (P<0.001), particularly in GC with increased (A) TNM stage (P<0.001), (B) lymph node metastasis (P<0.001), (C) invasion (P=0.004), (D) tumor diameter (P<0.001) and (E) distant metastasis (P=0.040). The expression of DLC1 was not significantly associated with (F) tumor differentiation (P=0.098), (G) age (P=0.814) or (H) gender (P=0.260). DLC1, deleted in liver cancer-1; GC, gastric cancer; TNM, tumor-node-metastasis.

Mentions: The protein expression status of DLC1 was detected using immunohistochemistry in all pairs of paraffin-embedded GC samples and matched para-cancerous gastric tissues. Representative staining examples of normal gastric tissues and DLC1-positive and -negative GC tissues are presented in Fig. 1. It was revealed that DLC1 was predominantly expressed in the cytoplasm, and the immunoreactivity score of DLC1 was significantly lower in the majority of the pairs of GC samples, compared with the matched para-cancerous tissues [73.61%; 212/288); P<0.001). As shown in Fig. 2A, DLC1 deficiency was more frequently observed in GC (75.69%; 218/288), compared with the corresponding noncancerous gastric tissues (21.18%; 61/288; P<0.001).


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 is frequently deficient in GC. (A) Negative expression of DLC1 was more frequently observed in GC samples, compared with the matched para-cancerous normal tissues (P<0.001), particularly in GC with increased (A) TNM stage (P<0.001), (B) lymph node metastasis (P<0.001), (C) invasion (P=0.004), (D) tumor diameter (P<0.001) and (E) distant metastasis (P=0.040). The expression of DLC1 was not significantly associated with (F) tumor differentiation (P=0.098), (G) age (P=0.814) or (H) gender (P=0.260). DLC1, deleted in liver cancer-1; GC, gastric cancer; TNM, tumor-node-metastasis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-12-04-5771: DLC1 is frequently deficient in GC. (A) Negative expression of DLC1 was more frequently observed in GC samples, compared with the matched para-cancerous normal tissues (P<0.001), particularly in GC with increased (A) TNM stage (P<0.001), (B) lymph node metastasis (P<0.001), (C) invasion (P=0.004), (D) tumor diameter (P<0.001) and (E) distant metastasis (P=0.040). The expression of DLC1 was not significantly associated with (F) tumor differentiation (P=0.098), (G) age (P=0.814) or (H) gender (P=0.260). DLC1, deleted in liver cancer-1; GC, gastric cancer; TNM, tumor-node-metastasis.
Mentions: The protein expression status of DLC1 was detected using immunohistochemistry in all pairs of paraffin-embedded GC samples and matched para-cancerous gastric tissues. Representative staining examples of normal gastric tissues and DLC1-positive and -negative GC tissues are presented in Fig. 1. It was revealed that DLC1 was predominantly expressed in the cytoplasm, and the immunoreactivity score of DLC1 was significantly lower in the majority of the pairs of GC samples, compared with the matched para-cancerous tissues [73.61%; 212/288); P<0.001). As shown in Fig. 2A, DLC1 deficiency was more frequently observed in GC (75.69%; 218/288), compared with the corresponding noncancerous gastric tissues (21.18%; 61/288; P<0.001).

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