Potential of extravasated platelet aggregation as a surrogate marker for overall survival in patients with advanced gastric cancer treated with preoperative docetaxel, cisplatin and S-1: a retrospective observational study

Abstract

BackgroundThe theory of extravasated platelet aggregation in cancer lesions was recently introduced. We investigated the association of platelet aggregation in gastric cancer stroma with clinicopathological features, chemotherapeutic response, pathological response, and survival.MethodsThe study comprised 78 patients with advanced gastric cancer who had undergone gastrectomy with or without combination of docetaxel, cisplatin and S-1 (DCS) as preoperative chemotherapy between 2005 and 2014. The patients were divided into two groups: patients who had received preoperative DCS therapy forming the p-DCS group and patients who had not received preoperative DCS therapy forming the control group. The 39 patients in the control group had received gastrectomy and postoperative chemotherapy of S-1 alone. Platelet aggregation in biopsy specimens before preoperative DCS therapy in the p-DCS group and at the time of diagnosis in the control group were evaluated using CD42b immunohistochemical staining.ResultsTwenty-four patients in the p-DCS group and 19 in the control group were found to have platelet aggregation in their cancer stroma. Patients with histologically confirmed platelet aggregation had significantly higher rates of chemoresistance (58.3%) than those without platelet aggregation (20.0%) (P = 0.019). According to multivariate analysis, CD42b expression (odds ratio: 5.102, 95% confidence interval: 1.039–25.00, P = 0.045) was correlated with chemoresistance. CD42b expression and histological non-responder status were both significantly correlated with poor overall survival (OS) (P = 0.012, P = 0.016); however, RECIST was not correlated with OS. In the control group, CD42b expression was also significantly correlated with poor overall survival (OS) (P = 0.033). In the p-DCS group, according to multivariate analysis, male sex (hazard ratio: 0.281, 95% confidence interval: 0.093–0.846, P = 0.024) was correlated with good prognosis and CD42b expression (hazard ratio: 4.406, 95% confidence interval: 1.325–14.65, P = 0.016) with poor prognosis.ConclusionsThis study suggests that platelets in gastric cancer stroma may create a favorable microenvironment for chemoresistance. CD42b immunohistochemical staining of biopsy specimens is a promising candidate for being a prognostic marker in patients with gastric cancer.

<p>Peripheral Blood Platelet–Lymphocyte Ratio Is Good Predictor of Chemosensitivity and Prognosis in Gastric Cancer Patients</p>

“…[24][25][26] However, the related mechanism of action remains largely unknown. 4 Although PLR, NLR, and other hematological markers including nutrition indicators have been established as effective prognostic factors for numerous types of cancers, [8][9][10][11] the relationship between these markers and chemotherapy resistance is also unclear.…”

“…We have previously reported that a primary lesion with platelet infiltration as CD42b positive cells revealed chemo-resistance. 4 We focused on the role of circulating platelets in this study. Circulating platelets attach and aggregate to the vascular wall via von Willebrand factor (vWF), which released from damaged endothelial cells by cisplatin-based chemotherapy.…”

“…Extravascular platelets deposited in the cancer microenvironment have been reported as a short-term prognostic factor and are related to anticancer drug resistance. 4 These effects are thought to be a result of microparticles from activated platelets, such as vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), both of which promote tumor development. Many reports identify platelets as cancer development factors, [5][6][7] however, immunostaining is required for identifying extravascular platelets.…”

The Role of Platelet-Derived ADP and ATP in Promoting Pancreatic Cancer Cell Survival and Gemcitabine Resistance

“…Various types of cancer cells, including PDAC cells, can activate platelets, which in turn, can support tumour cell growth and metastasis [ 10 , 42 , 43 , 44 ]. Recent clinical studies have indicated an association between platelets and poor chemotherapeutic responses in cancer patients [ 45 , 46 ]. However, the mechanisms by which platelets confer chemoresistance to cancer cells have remained unclear.…”

Extravasated platelet aggregation contributes to tumor progression via the accumulation of myeloid‑derived suppressor cells in gastric cancer with peritoneal metastasis

“…We previously found a correlation between extravasated platelet aggregation (EPA) and epithelial-mesenchymal transition (EMT) in breast cancer, and showed that patients with EPA were less responsive to neo-adjuvant chemotherapy ( 10 ). Furthermore, EPA in primary gastric cancer biopsy specimens was inversely correlated with pathological response to preoperative chemotherapy, and was identified as an independent prognostic factor ( 11 ).…”