Effect of pravastatin on the survival of patients with advanced gastric cancer

Bujanda, Luís; Rodríguez-González, Araceli; Sarasqueta, Cristina; Eizaguirre, Emma; Hijona, Elizabeth; Marín, José J.G.; Cosme, Ángel

doi:10.18632/oncotarget.6777

Cited by 15 publications

(15 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates hope as a possible adjuvant therapy agent for GCa patients. There has been some success of using statins in preclinical GCa models , but most clinical trials have failed . In this study, we found that HMGCR is not a positive promoter for GCa progression.…”

Section: Discussionmentioning

confidence: 61%

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Chang

Cheng

et al. 2018

Cancer Medicine

View full text Add to dashboard Cite

Cholesterol affects cancer progression, and acetyl‐CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl‐CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan–Meier Plotter web‐based gene survival analyzer and The Cancer Genome Atlas (TCGA)‐database analyzed with DBdriver.v2 platform, we revealed acetyl‐CoA production and the mevalonate pathway are associated with GCa prognosis. We found mitochondrial‐derived acetyl‐CoA contributing enzymes (acyl‐coA synthetase super‐family 3; ACSS3) is the GCa progression confounder. Interestingly, it is not HMGCR (the committee enzyme of mevalonate pathway), but lower mevalonate pathway enzymes (e.g., MVK, LSS, DHCR14A1, SC4MOL, HSD17B7, SC5D) promote GCa patients 5‐years overall survival in a differential level. Advanced analyses found ACSS3 is prognosis biosignatures for multiple GCa disease conditions. This report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions, which implicates a targeting value for GCa therapy. While knockdown ACSS3 could suppress growth and invasion of GCa cells, of which even more impactful under starvation condition. This is the first report, surprisingly, revealed ACSS3 as important cancer prognosis biomarker. Targeting ACSS3 could be a novel therapeutic strategy for cancer, in this case, GCa.

show abstract

Section: Discussionmentioning

confidence: 61%

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Chang

Cheng

et al. 2018

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…A 2014 Korean phase three trial randomly allocated 244 Stage 4 gastric patients to simvastatin 40 mg daily or placebo finding little evidence of difference in progression‐free survival in the simvastatin group compared with placebo (HR 0.93; 95% CI, 0.68‐1.26) . Similarly, a nonrandomised prospective study from Spain found no difference in survival for Stage 3 or 4 patients with gastric cancer, 20 of whom were allocated to receive pravastatin and 40 to placebo . A Korean observational study investigated recurrence‐free survival and all‐cause mortality in 241 patients with Stage 2 and 3 gastric cancer undergoing radical gastrectomy.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, several observational studies showed reductions in gastric cancer risk with statin use . Four studies have investigated statin use postgastric cancer diagnosis and survival; however, these were not population‐based, limited by small‐size (largest study contained 244 patients) and were generally conducted in specific subgroups of gastric cancer patients (for instance, Stage 4 patients). Furthermore, results were conflicting, with one study observing an 83% reduction in all‐cause mortality with 6 months of statin use whilst others observed little evidence of improved outcomes …”

Section: Introductionmentioning

confidence: 99%

“…8 In addition, several observational studies showed reductions in gastric cancer risk with statin use. [11][12][13] Four studies [14][15][16][17] have investigated statin use postgastric cancer diagnosis and survival; however, these were not population-based, limited by small-size (largest study contained 244 patients 15 ) and were generally conducted in specific subgroups of gastric cancer patients (for instance, Stage 4 patients 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, results were conflicting, with one study 14 observing an 83% reduction in all-cause mortality with 6 months of statin use whilst others observed little evidence of improved outcomes. [15][16][17] We conducted a study using two independent population-based cohorts of patients with gastric cancer to determine the association between statin use and gastric cancer-specific mortality.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Spence

Busby

Hughes

et al. 2018

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

Purpose Preclinical studies show statins inhibit pathways involved in gastric cancer progression, with observational studies demonstrating reduced gastric cancer risk in statin users. However, few studies have investigated statin use and survival in gastric cancer. We investigated statin use and survival in two large population‐based gastric cancer cohorts. Methods Patients diagnosed with gastric cancer from 1998 to 2012 were identified from English and Scottish cancer registries. Statin prescriptions were identified from linkages to the UK Clinical Practice Research Datalink in England and the Prescribing Information System in Scotland, and deaths identified from national mortality records. Time‐dependent Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer‐specific mortality by statin use in multivariate analysis. Meta‐analysis techniques pooled results across the cohorts. Results The combined cohorts contained 3833 patients with gastric cancer and 2392 cancer‐specific deaths. Statin use after diagnosis was associated with reduced cancer‐specific mortality (adjusted HR 0.83; 95% CI, 0.74‐0.92). HRs for less than 1 year and over 1 year of statin use were similar (adjusted HR 0.83; 95% CI, 0.73‐0.94 and adjusted HR 0.83; 95% CI, 0.64‐1.01, respectively). Statin use prior to diagnosis was also associated with reduced cancer‐specific mortality (adjusted HR 0.91; 95% CI, 0.84‐0.98). Conclusions In two independent UK cohorts, there was some evidence that statin use was associated with reduced cancer‐specific mortality. However, these associations were weak in magnitude and did not follow a clear dose response, and we cannot rule out confounding by stage.

show abstract

Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study

Holmberg,

Kauppila,

Asplund

et al. 2024

Gastric Cancer

View full text Add to dashboard Cite

Background Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. Methods This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality. Results Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82–1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79–1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1. Conclusions Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.

show abstract

Effect of pravastatin on the survival of patients with advanced gastric cancer

Cited by 15 publications

References 26 publications

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study

Contact Info

Product

Resources

About