The Ratio of the Hemoglobin to Red Cell Distribution Width Combined with the Ratio of Platelets to Lymphocytes Can Predict the Survival of Patients with Gastric Cancer Liver Metastasis.

BACKGROUND: Hemoglobin/red cell distribution width (HR) and platelet/lymphocyte (PLR) ratios are considered effective prognostic markers in various cancers. We have proposed a new prognostic parameter: HR+PLR. The aim of this study is to explore the prognostic value of the HR+PLR scoring system in patients with gastric cancer liver metastasis. METHODS: This study retrospectively analyzed the clinical data of 306 patients with gastric cancer liver metastases admitted to our hospital from 2007 to 2014. According to the size of HR value and PLR value, we will divide the patients into three groups, namely, HR+PLR: (1) 0 points: HR > 1.02 and PLR < 128; (2) 1 point: HR > 1.02 and PLR > 128 and HR < 1.02 and PLR < 128; and (3) 2 points: HR < 1.02 and PLR > 128. RESULTS: The HR+PLR score was statistically different from age (P = 0.049), T stage (P < 0.001), N stage (P = 0.017), number of liver metastases (P = 0.018), gastrectomy (P < 0.001), hepatectomy (P = 0.001), peritoneal metastasis (P = 0.012), prognostic nutritional index (PNI) (P = 0.028), and neutrophil/lymphocyte ratio (NLR) (P = 0.045). The HR+PLR scoring system has a higher area under the ROC curve (AUC value) than PNI, PLR, HR, and PLR (AUC = 0.798, P < 0.001). In multivariate analysis, gastrectomy (P = 0.001), hepatectomy (P < 0.001), chemotherapy (P = 0.014), and HR+PLR score (P < 0.001) were considered independent prognostic factors. CONCLUSION: For patients with gastric cancer liver metastasis, the HR+PLR score is a simple, reliable, and economic prognostic marker.

Changing trends of clinicopathologic features and survival duration after surgery for gastric cancer in Northeast China.

BACKGROUND: Through analyzing the data from a single institution in Northeast China, this study revealed the possible clinicopathologic characteristics that influence the prognosis of patients with gastric cancer (GC). AIM: To evaluate the changing trends of clinicopathologic features and survival duration after surgery in patients with GC in Northeast China, which is a high-prevalence area of GC. METHODS: The study analyzed the difference in clinicopathologic features and survival duration after surgery of 5887 patients who were histologically diagnosed with GC at the Harbin Medical University Cancer Hospital. The study mainly analyzed the data in three periods, 2000 to 2004 (Phase 1), 2005 to 2009 (Phase 2), and 2010 to 2014 (Phase 3). RESULTS: Over time, the postoperative survival rate significantly increased from 2000 to 2014. In the past 15 years, compared with Phases 1 and 2, the tumor size was smaller in Phase 3 (P < 0.001), but the proportion of high-medium differentiated tumors increased (P < 0.001). The proportion of early GC gradually increased from 3.9% to 14.4% (P < 0.001). A surprising improvement was observed in the mean number of retrieved lymph nodes, ranging from 11.4 to 27.5 (P < 0.001). The overall 5-year survival rate increased from 24% in Phase 1 to 43.8% in Phase 3. Through multivariate analysis, it was found that age, tumor size, histologic type, tumor-node-metastasis stage, depth of invasion, lymph node metastasis, surgical approach, local infiltration, radical extent, number of retrieved lymph nodes, and age group were independent risk factors that influenced the prognosis of patients with GC. CONCLUSION: The clinical features of GC in Northeast China changed during the observation period. The increasing detection of early GC and more standardized surgical treatment effectively prolonged lifetimes.

Preoperative Systemic Immune-Inflammation Index (SII) for Predicting the Survival of Patients with Stage I-III Gastric Cancer with a Signet-Ring Cell (SRC) Component.

BACKGROUND: Recently, a novel systemic immune-inflammation index (SII) based on peripheral lymphocytes, neutrophils, and platelets has been reported to be correlated with patient prognosis in several malignancies, including gastric cancer. However, the prognostic value of the SII for gastric cancer patients with a signet-ring cell (SRC) component has not yet been reported. In this study, we aimed to assess the prognostic value of the SII in gastric cancer patients with an SRC component after curative resection. METHODS: This study was a retrospective analysis of 512 GC patients with an SRC component who underwent curative resection. The prognostic value of the SII was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: In our study cohort, an optimal cut-off value for the SII of 527 was used to stratify patients with gastric cancer (GC) into low (<527) and high SII (≥527) groups. Our study indicated that a high SII (≥527) was significantly correlated with a large tumor size (p < 0.001), infiltration of serosa (p < 0.001), lymph node metastasis (p < 0.001), and advanced TNM stage (p < 0.001). Univariate and multivariate analyses further demonstrated that a low SII was correlated with better clinical outcome and was an independent prognostic predictor in GC patients with an SRC component. Furthermore, the SII retained prognostic value in the subgroup analysis, including subgroup of different TNM stages and pure or mixed signet-ring cell carcinomas (SRCCs). CONCLUSION: The SII is a simple, promising, and practical prognostic biomarker for patients with surgically resected mixed SRCC and pure SRCC. The SII could complement current prognostic tools for better treatment planning and stratification of patients.

CircPIP5K1A facilitates gastric cancer progression via miR-376c-3p/ZNF146 axis.

BACKGROUND: Recently, many emerging circular RNAs (circRNAs) have been studied in human malignancies, including gastric cancer (GC). Researches concerning cancers have revealed that aberrant expression of circRNAs play a big part in tumorigenesis and development of diverse malignant tumors. Although hsa_circ_0014130 (circPIP5K1A) has been confirmed to be closely related to non-small cell lung cancer (NSCLC) progression, the knowledge of its function on GC progression remains unclear. Therefore, it is of great interest to uncover the underlying role of circPIP5K1A in GC. METHODS: The expression and characteristic of circPIP5K1A were separately analyzed by RT-qPCR, nucleic acid electrophoresis, RNase R and Actinomycin D treatment. CCK-8, colony formation, EdU, transwell, TUNEL, flow cytometry, luciferase reporter, RIP and RNA pull-down assays were employed to testify the regulatory role of circPIP5K1A in GC. RESULTS: In current study, circPIP5K1A, featured with closed-loop structure, was proved to be highly expressed in tissues and cells of GC. Loss-of-function assays depicted that silencing circPIP5K1A suppressed GC development. Follow-up mechanism tests unveiled that circPIP5K1A bound with miR-376c-3p and inhibition of miR-376c-3p reversed circPIP5K1A downregulation-mediated effect on GC progression. Additionally, ZNF146 was verified to be the downstream molecule of circPIP5K1A/miR-376c-3p axis in modulating GC progression. CONCLUSIONS: circPIP5K1A stimulates GC progression by sponging miR-376c-3p to upregulate ZNF146 expression.

CD66b+ neutrophils and α-SMA+ fibroblasts predict clinical outcomes and benefits from postoperative chemotherapy in gastric adenocarcinoma.

BACKGROUND: Emerging evidence indicates that the tumor microenvironment (TME) influences tumor progression through the various cells it contains. Tumor-associated neutrophils (TANs) and cancer-associated fibroblasts (CAFs) are prominent constituents of diverse malignant solid tumors and are crucial in the TME and cancer evolution. However, the relationships and combined prognostic value of these two cell types are not known in gastric adenocarcinoma (GAC). MATERIALS AND METHODS: In total, 215 GAC patients who underwent curative surgery were enrolled. TANs were assessed by immunohistochemical staining for CD66b, and CAFs were evaluated by immunohistochemical staining for α-smooth muscle actin (α-SMA). RESULTS: The percentages of patients with high-density TANs and CAFs in GAC tissue were 47.9% (103/215) and 43.3% (93/215), respectively. The densities of TANs and CAFs in GAC tissue samples were markedly elevated and independently correlated with GAC clinical outcomes. A strong correlation (R = .348, P < .001) was detected between TANs and CAFs in GAC. The combination of TANs and CAFs produced a more exact outcome than either factor alone. Patients with an α-SMAlow CD66bhigh (hazard ratio [HR] = 1.791; 95% CI: 1.062-3.021; P = .029), α-SMAhigh CD66blow (HR = 2.402; 95% CI: 1.379-4.183; P = .002), or α-SMAhigh CD66bhigh (HR = 3.599; 95% CI: 2.330-5.560; P < .001) phenotype were gradually correlated with poorer disease-free survival than the subset of patients with an α-SMAlow CD66blow phenotype. The same results were observed for disease-specific survival in the subgroups. Noticeably, in stage II-III patients with the α-SMAlow CD66blow phenotype, an advantage was obtained with postoperative chemotherapeutics, and the risk of a poor prognosis was reduced compared with stage II-III patients with the α-SMAlow CD66bhigh , α-SMAhigh CD66blow or α-SMAhigh CD66bhigh phenotype (HR: 0.260, 95% CI: 0.124-0.542, P < .001 for disease-free survival; and HR: 0.258, 95% CI: 124-0.538, P < .001 for disease-specific survival). CONCLUSION: Overall, we concluded that the combination of CD66b+ TANs and α-SMA+ CAFs could be used as an independent factor for patient outcomes and to identify GAC patients who might benefit from the administration of postoperative chemotherapeutics.

Estrogen facilitates gastric cancer cell proliferation and invasion through promoting the secretion of interleukin-6 by cancer-associated fibroblasts.

As a common disease, gastric cancer (GC) has influenced over 1 million people worldwide. Despite of prevention and optimal treatments, GC still has a high mortality. The role of cancer-associated fibroblasts (CAFs) in tumor progression has recently attracted attention, yet few studies have focused on GC. Estrogen has been reported to relate to the poor prognosis of GC. Therefore, we investigated whether estrogen can stimulate CAFs to produce tumor promoting factors in this study. Gastric CAFs were isolated from GC tissues and treated with estrogen. ELISA results suggested that CAFs produced interleukin-6 (IL-6) after estrogen treatment in a dose-dependent manner. The cell culture supernatant for estrogen-treated CAFs was collected and used as conditioned medium (CM) for GC cells. After cultured in CM, increased cell proliferation and alteration of cell cycle were detected by CCK-8 assay, BrdU assay, and flow cytometry. Western blot and gelatin zymography were used to determine cancer invasion-associated proteins. Results indicated that the expression of matrix metalloproteinase 2 (MMP2) and MMP9 were enhanced by Estrogen-CAFs-CM. Additional transwell assay showed that cell invasion and migration were promoted after cultured in CM. Lastly, western blot and immunofluorescence results demonstrated that the level of phosphorylated signal transducer and activator of transcription 3 (STAT3) in GC cells increased after cultured in CM. The effect was neutralized by IL-6 neutralizing antibody and STAT3 siRNA. Conclusively speaking, estrogen can activate CAFs to produce IL-6, ending up with promotion of GC cell proliferation and invasion. This result may suggest a new therapeutic target for GC.

The combination of preoperative fibrinogen and neutrophil-lymphocyte ratio is a predictive prognostic factor in esophagogastric junction and upper gastric cancer.

Objective: Cancer-associated systemic inflammation response and hyperfibrinogenemia play crucial roles in cancer progression and prognosis. In this study, we assessed the clinical value of the preoperative fibrinogen and the neutrophil-lymphocyte ratio (NLR) in patients with adenocarcinoma of the esophagogastric junction (AEG) and upper gastric cancer (UGC). Methods: Patients with AEG or UGC who underwent curative surgery were divided into a training set (n=161) and a validation set (n=195). Univariate and multivariate Cox analyses were performed to evaluate the prognostic indicators for overall survival (OS). The optimization cut-off values for fibrinogen and the NLR were 3.09g/L and 1.84, respectively. The combination of fibrinogen and NLR (F-NLR) was 2 for patients with high fibrinogen (≥3.09g/L) and elevated NLR (≥1.84), whereas those with one or neither were indexed as 1 or 0, respectively. Results: F-NLR was identified as an independent prognostic indicator for OS in the training set (P=0.007) which was confirmed in the validation set (P=0.003). In the subgroup analyses, the prognostic significance of F-NLR was still maintained for stages I-II (P = 0.030 in the training set; and P =0.020 in the validation set) and III (P = 0.001 in the training set; and P <0.001 in the validation set).Notably, among patients with F-NLR 2 could benefit from adjuvant chemotherapy compared with those with F-NLR 0-1 (P = 0.020 in the training set; and P =0.005 in the validation set). Conclusions: The preoperative F-NLR score is an independent prognosis indicator for patients with AEG and UGC. And it may help clinicians to identify those patients who at high prognostic risk and will benefit from planning individualized treatment strategies.

Correction to: Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells.

.

Peripheral Venous Blood Platelet-to-Lymphocyte Ratio (PLR) for Predicting the Survival of Patients With Gastric Cancer Treated With SOX or XELOX Regimen Neoadjuvant Chemotherapy.

BACKGROUND: Inflammation plays an important role in tumor progression. Predicting survival is remarkably difficult in patients with gastric cancer receiving neoadjuvant chemotherapy. The aim of the present study is to investigate the potential prognostic significance of the platelet-to-lymphocyte ratio in patients with gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen. METHODS: Ninety-one patients with gastric cancer treated with neoadjuvant chemotherapy were enrolled in this study and then underwent operation. The optimal cutoff value was calculated using receiver-operating characteristic curve analyses. The optimal cutoff value of platelet-to-lymphocyte ratio was divided into low platelet-to-lymphocyte ratio <162 group and high platelet-to-lymphocyte ratio ≥162 group. Kaplan-Meier method and log-rank test were used to analyze the survival curves. The independent prognostic factors and prognostic value of the platelet-to-lymphocyte ratio were assessed by univariate and multivariate Cox proportional hazards regression model. The toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria. RESULTS: Kaplan-Meier analyses revealed that patients with low platelet-to-lymphocyte ratio correlated remarkably with better mean disease-free survival and mean overall survival than those with high platelet-to-lymphocyte ratio (mean disease-free survival 47.33 and 33.62 months, respectively; mean overall survival 51.21 and 36.80 months, respectively). The results demonstrated that platelet-to-lymphocyte ratio had prognostic significance using the cutoff value of 162 on disease-free survival and overall survival, and the mean disease-free survival and overall survival time for patients with low platelet-to-lymphocyte ratio were longer than those with high platelet-to-lymphocyte ratio. Meanwhile, patients with gastric cancer who had lower platelet-to-lymphocyte ratio had longer 1-, 3-, and 5-year rates of disease-free survival and overall survival. Moreover, patients with low platelet-to-lymphocyte ratio had longer mean disease-free survival and overall survival than those with high platelet-to-lymphocyte ratio in receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen. CONCLUSIONS: The preoperative platelet-to-lymphocyte ratio may be a promising and convenient prognostic biomarker for patients gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen neoadjuvant chemotherapy. It may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.

Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells.

PURPOSE: Epithelial to mesenchymal transition (EMT) can contribute to gastric cancer (GC) progression and recurrence following therapy. Tumor-associated neutrophils (TANs) are associated with poor outcomes in a variety of cancers. However, it is not clear whether TANs interact with the EMT process during GC development. METHODS: Immunohistochemistry was performed to examine the distribution and levels of CD66 + neutrophils in samples from 327 patients with GC. CD66b + TANs were isolated either directly from GC cell suspensions or were conditioned from healthy donor peripheral blood polymorphonuclear neutrophils (PMNs) stimulated with tumor tissue culture supernatants (TTCS) and placed into co-culture with MKN45 or MKN74 cells, after which migration, invasion and EMT were measured. Interleukin-17a (IL-17a) was blocked with a polyclonal antibody, and the STAT3 pathway was blocked with the specific inhibitor AG490. RESULTS: Neutrophils were widely distributed in gastric tissues of patients with GC and were enriched predominantly at the invasion margin. Neutrophil levels at the invasion margin were an independent predictor of poor disease-free survival (DFS) and disease-specific survival (DSS). IL-17a + neutrophils constituted a large portion of IL-17a-producing cells in GC, and IL-17a was produced at the highest levels in co-culture compared with that in TANs not undergoing co-culture. TANs enhanced the migration, invasion and EMT of GC cells through the secretion of IL-17a, which activated the Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3) pathway in GC cells, while deprivation of IL-17a using a neutralizing antibody or inhibition of the JAK2/STAT3 pathway with AG490 markedly reversed these TAN-induced phenotypes in GC cells induced by TANs. CONCLUSIONS: Neutrophils correlate with tumor stage and predict poor prognosis in GC. TANs produce IL-17a, which promotes EMT of GC cells through JAK2/STAT3 signalling. Blockade of IL-17a signalling with a neutralizing antibody inhibits TAN-stimulated activity in GC cells. Therefore, IL-17a-targeted therapy might be used to treat patients with GC.

The Fibrinogen to Mean Platelet Volume Ratio Can Predict Overall Survival of Patients with Non-Metastatic Gastric Cancer.

PURPOSE: Fibrinogen and platelets have been reported to play important roles in tumorigenesis and cancer progression. The aim of this research was to investigate the combination of functions of fibrinogen, platelets, and mean platelet volume (MPV) in predicting the survival of patients with gastric cancer (GC). MATERIALS AND METHODS: A retrospective study was conducted with 1,946 patients with GC and 299 patients with benign gastric tumor to analyze their fibrinogen, platelet, and MPV levels, and other clinicopathological characteristics along with their prognoses. Several indicators were evaluated along with fibrinogen, platelets, and MPV and their prognostic abilities were assessed. Univariate and multivariate survival analyses were conducted to determine the independent risk factors for overall survival. RESULTS: Increased levels of fibrinogen, platelets, and MPV were observed with the progress of the GC stages. Elevated fibrinogen, platelets, and the combined indicators, including fibrinogen*MPV (FM), platelet*fibrinogen*MPV (PFM), fibrinogen/MPV (FMR), platelet*fibrinogen (PF), platelet*fibrinogen/MPV (PFMR), platelet*MPV (PM), and platelet/MPV (PMR), foreboded poor prognosis. Meanwhile fibrinogen and FMR can be considered as independent risk factors for overall survival in patients with non-metastatic GC. But these indicators can hardly predict survival of patients in stage IV. CONCLUSIONS: Elevated fibrinogen, platelets, and MPV levels were in accordance with advanced stages, and fibrinogen, platelet, and MPV, in combination, can be used to predict survival of patients with non-metastatic GC. FMR was an independent prognostic factor for overall survival of patients with GC.

Systemic immune-inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy.

BACKGROUND AND OBJECTIVE: A novel systemic immune-inflammation index named SII (SII=N×P/L), which is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, has emerged and reflects comprehensively the balance of host inflammatory and immune status. We aimed to evaluate the potential prognostic significance of SII in patients with advanced gastric cancer who received neoadjuvant chemotherapy. SUBJECTS AND METHODS: The retrospective analysis included data from 107 patients with advanced gastric cancer undergoing neoadjuvant chemotherapy and 185 patients with pathology-proven gastric cancer. The optimal cutoff value of SII by receiver operating characteristic curve stratified patients into low SII (<600×109/L) and high SII (SII ≥600×109/L) groups. The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier survival curves and compared using log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SII. RESULTS: The results indicated that SII had prognostic significance using the cutoff value of 600×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Low SII was associated with prolonged DFS and OS, and the mean DFS and OS for patients with low SII were longer than for those with high SII (57.22 vs 41.56 months and 62.25 vs 45.60 months, respectively). Furthermore, we found that patients with low SII had better 1-, 3- and 5-year rates of DFS and OS than those with high SII. In addition, patients with low SII were likely to receive DFS and OS benefits from neoadjuvant chemotherapy and postoperative chemotherapy. CONCLUSION: SII may qualify as a noninvasive, cost-effective, convenient and reproducible prognostic indicator for patients with advanced gastric cancer undergoing neoadjuvant chemotherapy. It may help clinicians to identify those patients who will benefit from treatment strategy decisions.

Clinicopathological features and prognoses in younger and older patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Patients of different ages with gastric cancer (GC) have different clinicopathological features and prognoses. The results for different crowds are limited and controversial. The aim of this study was to investigate the differences in clinicopathological features and prognoses between younger and older GC patients. METHODS: From January 2007 to December 2011, a consecutive total of 112 GC patients under 41 years old and 358 GC patients over 69 years old who underwent gastrectomy for GC were recruited for this study. Then, the clinicopathological features and prognoses of these patients were analyzed comparatively. RESULTS: The gender, differentiation, carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly different between younger and older GC patients. There were more female and undifferentiated younger GC patients, and there were higher percentages of positive CA19-9 and CEA in older GC patients. The number of metastatic lymph nodes was an independent risk parameter for prognosis in younger patients, and the AJCC TNM (Tumor-Nodes-Metastases classification by American Joint Committee on Cancer) stage, radicality and tumor size were independent risk parameters for prognosis in older GC patients. Younger GC patients have a much better prognoses with lower monocyte-to-lymphocyte ratio and higher prognostic nutritional index than older patients. CONCLUSIONS: Younger GC patients have better immunity and nutritional status and better prognoses. The number of metastatic lymph nodes was the only risk parameter for prognosis in younger GC patients. We should take more effective treatments for younger GC patients with lymph nodes metastasis and pay more attention to the nutritional problems of older GC patients.

[Impact of preoperative lymphocyte to monocyte ratio on the prognosis of the elderly patients with stage II(-III( gastric cancer].

OBJECTIVE: To investigate the impact of preoperative lymphocyte to monocyte ratio on the prognosis of elderly patients with stage II(-III( gastric cancer. METHODS: Clinicopathological data of 188 patients with stage II(-III( gastric cancer aged≥75 years undergoing radical gastrectomy in our department from January 2007 to December 2011 were analyzed retrospectively. The optimal critical value of preoperative peripheral blood LMR in prediction of overall survival was determined through the receiver-operating characteristic (ROC) curve analysis. According to the critical value, patients were divided into the low LMR group and high LMR group. Clinicopathological features and prognosis were compared between the two groups. Univariate and multivariate analyses were performed to evaluate the clinical factors affecting prognosis with Cox proportional hazard model. RESULTS: ROC curve revealed the optimal critical value of preoperative peripheral blood LMR in prediction of overall survival was 4.34, then 71 cases were divided into the low LMR group (<4.34) and 117 cases into high LMR group (≥4.34). The low LMR group had greater tumor size (P=0.015) and higher level of carcinoembryonic antigen (CEA) (P=0.018) as compared to the high LMR group, and other clinicopathological parameters were not significantly different (all P>0.05). Median follow-up time of all the 188 patients was 21.8 (1.3 to 92.9) months. The 3-year survival rate of the low and high LMR groups was 36.8% and 45.1% respectively with significant difference (P=0.001). Univariate analysis revealed that the postoperative overall survival was associated with the preoperative LMR (P<0.001), absolute count of lymphocyte (P=0.002), absolute count of monocyte (P=0.016), CEA level (P=0.011), CA199 level (P=0.003), lymph node metastasis (P<0.001), tumor maximal size (P<0.001), TNM stage (P<0.001), postoperative adjuvant chemotherapy (P=0.004). Multivariate analysis revealed that the TNM stage III( (HR:2.708, 95%CI:1.356 to 5.411, P=0.005), tumor maximal size≥50 mm (HR: 1.737, 95%CI: 1.114 to 2.709, P=0.015), without postoperative adjuvant chemotherapy (HR: 0.651, 95%CI: 0.440 to 0.961, P=0.031), and preoperative peripheral blood LMR<4.34 (HR: 0.600, 95%CI: 0.376 to 0.958, P=0.032) were independent risk factors of prognosis. CONCLUSIONS: Preoperative peripheral blood LMR level possesses good predictive value of prognosis for the elderly patients with stage II(-III( gastric cancer. Low LMR is associated with poor outcomes.