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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 expression status in GC. (A) A total of 251 stage IB-III patients underwent radical resection and adjuvant chemotherapy. Among these patients, 185 were defied as DLC1 (−) and 66 were DLC1 (+). A total of 69 DLC1-(−) and 35 DLC1-(+) patients received FP-LOHP [FP-LOHP (+)] as adjuvant chemotherapy, while the remaining patients received alternative therapies [FP-LOHP (−)]. (B) Representative images of DLC1 immunohistochemical staining in para-cancerous normal tissues and GC tissues, observed under an optical microscope. Dashed boxes indicate the areas visualized at magnification, ×400 (on the right). DLC1, deleted in liver cancer-1; GC, gastric cancer; FP-LOHP, fluoropyrimidine-oxaliplatin combination therapy.
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f1-mmr-12-04-5771: DLC1 expression status in GC. (A) A total of 251 stage IB-III patients underwent radical resection and adjuvant chemotherapy. Among these patients, 185 were defied as DLC1 (−) and 66 were DLC1 (+). A total of 69 DLC1-(−) and 35 DLC1-(+) patients received FP-LOHP [FP-LOHP (+)] as adjuvant chemotherapy, while the remaining patients received alternative therapies [FP-LOHP (−)]. (B) Representative images of DLC1 immunohistochemical staining in para-cancerous normal tissues and GC tissues, observed under an optical microscope. Dashed boxes indicate the areas visualized at magnification, ×400 (on the right). DLC1, deleted in liver cancer-1; GC, gastric cancer; FP-LOHP, fluoropyrimidine-oxaliplatin combination therapy.

Mentions: A total of 288 patients were followed up for OS, which comprised 251 patients with stage IB-III GC and 37 patients with stage IV GC. The 251 patients with stage IB-III GC that underwent D2 gastrectomy and postoperative adjuvant chemotherapy were followed up for TTR. None of these patients received chemoradiation or preoperative chemotherapy. Among the patients who received adjuvant chemotherapy, 104 received FP-LOHP adjuvant chemotherapy, while the remaining 147 received regimens, which did not involve FP-LOHP combination (Fig. 1A). The ages of the patients ranged between 25 and 85 years (median, 52 years). The follow-up durations ranged between 0.5 and 79.0 months (median, 26.3 months). The clinicopathological characteristics of the patients are presented in Table I.


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 expression status in GC. (A) A total of 251 stage IB-III patients underwent radical resection and adjuvant chemotherapy. Among these patients, 185 were defied as DLC1 (−) and 66 were DLC1 (+). A total of 69 DLC1-(−) and 35 DLC1-(+) patients received FP-LOHP [FP-LOHP (+)] as adjuvant chemotherapy, while the remaining patients received alternative therapies [FP-LOHP (−)]. (B) Representative images of DLC1 immunohistochemical staining in para-cancerous normal tissues and GC tissues, observed under an optical microscope. Dashed boxes indicate the areas visualized at magnification, ×400 (on the right). DLC1, deleted in liver cancer-1; GC, gastric cancer; FP-LOHP, fluoropyrimidine-oxaliplatin combination therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-mmr-12-04-5771: DLC1 expression status in GC. (A) A total of 251 stage IB-III patients underwent radical resection and adjuvant chemotherapy. Among these patients, 185 were defied as DLC1 (−) and 66 were DLC1 (+). A total of 69 DLC1-(−) and 35 DLC1-(+) patients received FP-LOHP [FP-LOHP (+)] as adjuvant chemotherapy, while the remaining patients received alternative therapies [FP-LOHP (−)]. (B) Representative images of DLC1 immunohistochemical staining in para-cancerous normal tissues and GC tissues, observed under an optical microscope. Dashed boxes indicate the areas visualized at magnification, ×400 (on the right). DLC1, deleted in liver cancer-1; GC, gastric cancer; FP-LOHP, fluoropyrimidine-oxaliplatin combination therapy.
Mentions: A total of 288 patients were followed up for OS, which comprised 251 patients with stage IB-III GC and 37 patients with stage IV GC. The 251 patients with stage IB-III GC that underwent D2 gastrectomy and postoperative adjuvant chemotherapy were followed up for TTR. None of these patients received chemoradiation or preoperative chemotherapy. Among the patients who received adjuvant chemotherapy, 104 received FP-LOHP adjuvant chemotherapy, while the remaining 147 received regimens, which did not involve FP-LOHP combination (Fig. 1A). The ages of the patients ranged between 25 and 85 years (median, 52 years). The follow-up durations ranged between 0.5 and 79.0 months (median, 26.3 months). The clinicopathological characteristics of the patients are presented in Table I.

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