Background The neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) are representative blood markers of systemic inflammatory responses. However, the clinical significance of the combination of these markers is unclear. This study aimed to investigate the NLR and PLR in patients with advanced gastric cancer treated with chemotherapy and assess the clinical utility of a new blood score combining the NLR and PLR (NLR-PLR score) as a predictor of tumor response and prognosis. Methods We retrospectively analyzed 175 patients with gastric cancer receiving chemotherapy or chemoradiotherapy. These patients were categorized into progressive disease (PD) and non-PD groups according to tumor response. The NLR and PLR before treatment were examined, and the cut-off values were determined. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (> 2.461) and high PLR (> 248.4); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. Results With regard to tumor response, 64 and 111 patients had PD and non-PD, respectively. The NLR-PLR score was significantly higher in patients with PD than in those with non-PD ( p = 0.0009). The prognosis was significantly poorer in patients with a higher NLR-PLR score than in those with a lower NLR-PLR score ( p <  0.0001). Multivariate analysis demonstrated that the NLR-PLR score was an independent prognostic factor for prediction of overall survival ( p = 0.0392). Conclusion Low-cost stratification according to the NLR-PLR score might be a promising approach for predicting tumor response and prognosis in patients with advanced gastric cancer.

BACKGROUND The authors hypothesized that circulating tumor cells (CTCs) in patients with gastric cancer are associated with prognosis and disease recurrence. In this study, they evaluated CTCs in gastric cancer and clarified the clinical impact of CTCs. METHODS In total, 265 consecutive patients with gastric cancer were enrolled. Fourteen patients were excluded from the analysis, including 12 patients who another cancer and 2 patients who refused the treatment. The remaining 251 patients were divided into 2 groups: 148 patients who underwent gastrectomy (the resection group) and 103 patients who did not undergo gastrectomy (the nonresectable group). Peripheral blood samples were collected before gastrectomy or chemotherapy. A proprietary test for capturing, identifying, and counting CTCs in blood was used for the isolation and enumeration of CTCs. RESULTS CTCs were detected in 16 patients (10.8%) from the resection group and in 62 patients (60.2%) from the nonresectable group. The overall survival rate for the entire cohort was significantly lower in patients with CTCs than in those without CTCs (P < .0001). In the resection group, relapse‐free and overall survival in patients with CTCs was significantly lower than in patients without CTCs (P < .0001). It was noteworthy that the expression of CTCs was an independent factor for determining the overall survival of patients with gastric cancer in multivariate analysis (P = .024). In the nonresectable group, the overall survival rate was significantly lower in patients with CTCs than in those without CTCs (P = .0044). CONCLUSIONS The evaluation of CTCs in peripheral blood may be a useful tool for predicting tumor progression, prognosis, and the effect of chemotherapy in patients with gastric cancer. Cancer 2013;119:3984–3991. © 2013 American Cancer Society.

BackgroundEsophageal squamous cell carcinoma is an aggressive gastrointestinal tract cancer. To date, the presence of circulating tumor cells (CTC) has been reported as a prognostic factor in peripheral blood from patients with gastrointestinal cancers.MethodsThe CellSearch system was used to isolate and enumerate CTCs. A total of 90 patients with esophageal squamous cell carcinoma who received chemotherapy or chemoradiotherapy were enrolled. Peripheral blood specimens were collected before and after treatments.ResultsAt baseline analysis, CTCs were detected in 25 patients (27.8 %). Overall survival was significantly shorter in patients with than without CTCs. Follow-up blood specimens were obtained from 71 patients. Partial response, stable disease, and progressive disease after treatment were seen in 32, 12, and 27 patients, respectively. CTC positivity after treatment in the progressive disease group (40.7 %) was significantly higher than that of the partial response group (6.3 %). Patients with a change in CTC status from positive to negative had a good prognosis as well as patients without baseline CTCs.ConclusionsEvaluation of CTCs may be a promising indicator for predicting tumor prognosis and the clinical efficacy of chemotherapy or chemoradiation therapy in patients with esophageal squamous cell carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-015-4392-8) contains supplementary material, which is available to authorized users.

The clinical significance of B7-H3 expression in gastric cancer remains unclear, although the B7 ligand family plays a critical role in the T cell-mediated immune response. We therefore investigated B7-H3 expression as a blood marker of circulating tumor cells and determined correlations with tumor progression in patients with gastric cancer. B7-H3 expression in gastric cell lines was initially evaluated by immunocytochemistry. Furthermore, we used quantitative RT-PCR to assess B7-H3 mRNA expression in four cell lines and in 95 blood specimens from patients with gastric cancer, as well as in 21 samples of peripheral blood lymphocytes from healthy volunteers. B7-H3 expression in cell lines was identified by immunocytochemistry and quantitative RT-PCR. Blood specimens from patients with gastric cancer contained significantly more copies of B7-H3 mRNA than those from healthy volunteers without cancer (P < 0.0001). Levels of B7-H3 expression significantly correlated with overall stage (P = 0.013). The 5-year survival rate was significantly lower in patients with high B7-H3 expression than with low expression (P = 0.02). Multivariate analysis demonstrated that B7-H3 expression was an independent prognostic factor (P = 0.046). Our results indicate that B7-H3 appears to be a useful blood marker for predicting tumor progression in gastric cancer. (Cancer Sci 2011; 102: 1019-1024 G astric cancer is one of the most common gastrointestinal tract malignancies in Asia.(1-4) New anticancer agents such as S-1, taxanes, capecitabine, irinotecan and oxaliplatin have improved the prognosis of patients with unresectable advanced gastric cancer.(5-9) Nevertheless, the 5-year survival rates of patients with International Union Against Cancer (UICC) stage IIIA, IIIB, and IV gastric cancers are 30.8-54.0%, 16.1-36.5% and 9.2-23.9%, respectively.(10,11) Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are commonly used as established tumor markers in blood for patients with gastric cancer. However, the sensitivity and specificity of predicting tumor progression and postoperative recurrence are clinically insufficient and no molecular biomarkers can yet predict the prognosis of patients with gastric cancer. (12,13) The RT-PCR is a useful assay for detecting circulating tumor cells (CTC) within blood specimens from patients with various malignancies, including gastric cancer. (14)(15)(16)(17)(18) We reported that the presence of CTC correlates with tumor progression and outcomes of patients with esophageal, gastric and biliary-pancreatic cancer.(14-18) Several epithelial-specific antigens such as CEA, cytokeratin-19, and cytokeratin-20, have been used generally in many studies of CTC detection in gastric cancer. (15,19) However, recent studies have found false-positive results in RT-PCR assays using these markers for CTC detection. (20,21) Consequently, RT-PCR assays using conventional CTC markers have low specificity for detecting occult CTC from blood specimens. Furthermore, few candidate molecular blood markers of...

BackgroundThe transcription factor nuclear factor (erythroid-2)–related factor 2 (Nrf2) was originally identified as a critical regulator of intracellular anti-oxidants and of phase II detoxification enzymes through its transcriptional up-regulation of many anti-oxidant response element (ARE)-containing genes. Nrf2 protects not only normal cells but also cancer cells from cellular stress, and enhances cancer cell survival. Some studies have shown that Nrf2 expression in cancer patients has clinical significance. However, there has been no comprehensive analysis of the nuclear expression level of Nrf2 in gastrointestinal cancer cells. In this study we aimed to immunohistochemically evaluate the expression of Nrf2, and to assess its clinical significance in gastric cancer.MethodsA total of 175 gastric cancer patients who received R0 gastrectomy with standard lymph node dissection were enrolled. We immunohistochemically evaluated Nrf2 expression in the paraffin-embedded surgically resected specimens of these 175 patients. Group differences were analyzed using the χ2 test, Fisher’s exact test, and the Mann–Whitney U test. Associations between Nrf2 expression and clinicopathological features, including clinical outcome, were assessed using univariate and multivariate analyses, and Kaplan-Meier curves with the log-rank test, respectively.ResultsNrf2 immunoreactivity was predominantly identified in the nucleus of gastric cancer cells. Nrf2 positivity was closely associated with tumor size, tumor depth, lymph node metastases, lymphovascular invasion, histology and stage (p < 0.05 for all). A log-rank test indicated that the overall survival of the Nrf2-positive group was significantly poorer than that of the Nrf2-negative group (p < 0.01). And, positive Nrf2 expression was significantly associated with resistance to 5FU-based adjuvant chemotherapy (p = 0.024).ConclusionsNrf2 expression was positively associated with aggressive tumor behavior in gastric cancer. This result suggests that Nrf2 expression in gastric cancer is a potential indicator of worse prognosis.

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The evaluation of B7-H4 expression in blood is a useful tool for predicting the progression of gastric cancer and prognosis.

Abstract. Certain patients with early gastric cancer succumb to recurrent disease and cancer-associated complications. The key cause of recurrence is challenging to determine, since clinical blood markers that are able to predict the tumor properties of gastric cancer are limited. The present study investigated the fibrinogen concentration and neutrophil-lymphocyte ratio (NLR) in blood specimens from patients with gastric cancer, and assessed the clinical applicability of combining the fibrinogen concentration with the NLR (CFS-NLR) as a prognostic marker of gastric cancer. The present study consisted of 275 patients with gastric cancer, who were divided into three groups: Those possessing hyperfibrinogenemia (≥305 mg/dl) and a high NLR (≥2.34; CFS-NLR 2 group); those possessing either hyperfibrinogenemia or a high NLR (CFS-NLR 1 group); or those that possessed neither abnormality (CFS-NLR 0 group). The CFS-NLR was significantly associated with the depth of tumor invasion, lymph node metastasis, lymphovascular invasion and tumor stage (P<0.0001). The prognostic differences among the three groups were significant (P= 0.0016). Therefore, the CFS-NLR may be a potentially useful blood marker for predicting tumor progression and the prognosis of patients with gastric cancer.