ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood.

Numerous studies have reported that a variety of long noncoding RNAs (lncRNAs) can promote the proliferation, invasion, and migration of different tumor cells. However, different lncRNAs regulate cell functions in various forms, and the exact mechanisms are not clear. Here, we investigated the effect of the lncRNA ELF3-AS1 on gastric cancer (GC) cell function and explored the exact mechanism. Quantitative real-time polymerase chain reaction was used to detect the expression of ELF3-AS1 in GC tissues and adjacent nontumor tissues. Knockdown and overexpression of ELF3-AS1 was used to detect the effect of ELF3-AS1 on cell function. Potential downstream target genes were identified using RNA transcriptome sequencing, while RNA immunoprecipitation, chromatin immunoprecipitation, and Western blotting were performed to explore the tumor promotion mechanisms of ELF3-AS1. We observed that ELF3-AS1 was highly expressed in GC tissues, and high ELF3-AS1 expression predicted poor prognosis. The knockdown of ELF3-AS1 significantly inhibited cell proliferation, migration, and epithelial-mesenchymal transition and promoted apoptosis. Mechanistic investigations revealed that ELF3-AS1 may regulate the downstream target gene, C-C motif chemokine 20, by binding with the RNA-binding protein hnRNPK. Additionally, we found that high ELF3-AS1 expression was associated with thrombocytosis. Interleukin-6 and thrombopoietin may be involved in ELF3-AS1-induced paraneoplastic thrombocytosis. Together, our results demonstrate that aberrantly expressed ELF3-AS1 in GC may play important roles in oncogenesis and progression and is expected to become a new target for the diagnosis and treatment of GC.

The choice of tissue fixative is a key determinant for mass spectrometry imaging based tumor metabolic reprogramming characterization.

The application of mass spectrometry imaging (MSI) for the study of spatiotemporal alterations of the metabolites in tumors has brought a number of significant biological results. At present, metabolite profiling based on MSI is typically performed on frozen tissue sections; however, the majority of clinical specimens need to be fixed in tissue fixative to avoid autolysis and to preserve antigenicity. In this study, we present the global impacts of different fixatives on the MS imaging of gastric cancer tissue metabolites. The MSI performances of 17 kinds of metabolites, such as amino acids, polyamines, cholines, organic acids, polypeptides, nucleotides, nucleosides, nitrogen bases, cholesterols, fatty acids, and phospholipids, in untreated, 10% formalin-, 4% paraformaldehyde-, acetone-, and 95% ethanol-fixed gastric cancer tissues were thoroughly explored for the first time. Furthermore, we also investigated the spatial expressions of 6 metabolic enzymes, namely, GLS, FASN, CHKA, PLD2, cPLA2, and EGFR, closely related to tumor-associated metabolites. Immunohistochemical staining carried out on the same tissue sections' which have undergone MSI analysis' suggests that enzymatic characterization is feasible after metabolite imaging. Combining the spatial signatures of metabolites and pathway-related metabolic enzymes in heterogeneous tumor tissues offers an insight to understand the complex tumor metabolism. Graphical abstract.

Addition of peritonectomy to gastrectomy can predict good prognosis of gastric adenocarcinoma patients with intraoperatively proven single P1/P2 carcinomatosis.

This study was to evaluate the prognosis of peritonectomy following gastrectomy for gastric adenocarcinoma patients with intraoperatively proven single P1/P2 carcinomatosis and to define the best therapeutic strategy of the patient cohort. The patients with intraoperatively proven single P1/P2 carcinomatosis from a prospectively maintained database were divided into resection group and non-resection group based on complete gross resection of peritoneal carcinomatosis. From 2005 to 2012, there were 103 patients in the resection group and 122 patients in the non-resection group. There was no difference in morbidity and mortality between groups. The patients did not have improved median survival in P1 carcinomatosis compared to P2 carcinomatosis (15.53 vs 14.80 months, p = 0.450). The median survival was significantly improved in the resection group compared to the patients in the non-resection group (21.07 vs 13.37 months, p < 0.001). The patients undergoing complete gross peritonectomy plus postoperative chemotherapy had a significantly longer median survival than patients who had complete gross peritonectomy alone, patients receiving postoperative chemotherapy alone, and patients receiving neither peritonectomy nor postoperative chemotherapy (27.33 vs 12.00 vs 16.00 vs 10.33 months, p < 0.001). In the multivariate analysis, poor performance status ( p = 0.036), absence of complete gross peritonectomy ( p < 0.001), and lack of postoperative chemotherapy ( p < 0.001) were identified as independently associated with poor survival. The data indicate complete gross peritonectomy following gastrectomy confers a survival benefit to gastric cancer patients with intraoperatively proven single P1/P2 carcinomatosis. In addition, postoperative chemotherapy improves survival regardless of resection of peritoneal carcinomatosis and should be recommended.

Establishment of environment-sensitive probes targeting BRD3/BRD4 for imaging and therapy of tumor.

The BET (bromo and extra-terminal) family proteins are epigenetic readers and master transcription coactivators, which have attracted great interests as cancer therapeutic targets. However, there are few developed labeling toolkits that can be applied for the dynamic studies of BET family proteins in living cells and tissue slices. In order to label and study the distribution of the BET family proteins in tumor cells and tumor tissues, a novel series of environment-sensitive fluorescent probes (6a-6c) were designed and evaluated for their labeling properties. Interestingly, 6a is capable of identifying tumor tissue slices and making a distinction between the tumor and normal tissues. Moreover, it can localize to the nuclear bodies in tumor slices just like BRD3 antibody. In addition, it also played an anti-tumor role through the induction of apoptosis. All these features render 6a may compatible for immunofluorescent studies and future cancer diagnosis, and guide for the discovery of new anticancer drugs.

Small-molecule inhibitors of breast cancer-related targets: Potential therapeutic agents for breast cancer.

Despite dramatic advances in cancer research and therapy, breast cancer remains a tricky health problem and represents a top biomedical research priority. Nowadays, breast cancer is still the leading cause of malignancy-related deaths in women, and incidence and mortality rates of it are expected to increase significantly the next years. Currently more and more researchers are interested in the study of breast cancer by its arising in young women. The common treatment options of breast cancer are chemotherapy, immunotherapy, hormone therapy, surgery, and radiotherapy. Most of them require chemical agents, such as PARP inhibitors, CDK4/6 inhibitors, and HER2 inhibitors. Recent studies suggest that some targets or pathways, including BRD4, PLK1, PD-L1, HDAC, and PI3K/AKT/mTOR, are tightly related to the occurrence and development of breast cancer. This article reviews the interplay between these targets and breast cancer and summarizes the progress of current research on small molecule inhibitors of these anti-breast cancer targets. The review aims to provide structural and theoretical basis for designing novel anti-breast cancer agents.

Recent progress in agents targeting polo-like kinases: Promising therapeutic strategies.

Polo-like kinases (PLKs) play important roles in regulating multiple aspects of cell cycle and cell proliferation. In many cancer types, PLK family members are often dysregulated, which can lead to uncontrolled cell proliferation and aberrant cell division and has been shown to associate with poor prognosis of cancers. The key roles of PLK kinases in cancers lead to an enhanced interest in them as promising targets for anticancer drug development. In consideration of PLK inhibitors and some other anticancer agents, such as BRD4, EEF2K and Aurora inhibitors, exert synergy effects in cancer cells, dual-targeting of PLK and other cancer-related targets is regarded as an rational and potent strategy to enhance the effectiveness of single-targeting therapy for cancer treatment. This review introduces the PLK family members at first and then focuses on the recent advances of single-target PLK inhibitors and summarizes the corresponding SARs of them. Moreover, we discuss the synergisms between PLK and other anti-tumor targets, and sum up the current dual-target agents based on them.

A novel long noncoding RNA, TMEM92-AS1, promotes gastric cancer progression by binding to YBX1 to mediate CCL5.

Numerous studies have revealed that long noncoding RNAs (lncRNAs) with oncogene properties play vital roles in gastric cancer (GC). In this study, we aimed to elucidate the function of TMEM92-AS1 in GC progression and to investigate its underlying mechanisms. TMEM92-AS1 was filtered from the Gene Expression Omnibus database. GC tissues and adjacent normal tissues were used to detect the expression level of TMEM92-AS1. MTT, colony-formation assays, Edu, cell cycle, apoptosis and subcutaneous tumour formation assays were used to detect the role of TMEM92-AS1 in cell function. RNA transcriptome sequencing was used to seek downstream target genes. Reverse transcription (RT)-qPCR, western blot, RNA and chromatin immunoprecipitation assays were used to investigate the mechanisms involved. TMEM92-AS1 was significantly overexpressed in GC tissues and correlated with poor overall survival and disease-free survival. Furthermore, TMEM92-AS1 promoted GC cell proliferation and migration in vitro and tumorigenic ability in vivo. RNA transcriptome sequence analysis revealed a potential downstream target gene, C-C motif chemokine ligand 5 (CCL5), and a mechanistic study found that TMEM92-AS1 regulated CCL5 by binding to the transcription factor Y-box binding protein 1(YBX1), which has oncogene properties. In addition, TMEM92-AS1 was found to be associated with peripheral blood leukocyte counts, especially neutrophils. Further investigation found that TMEM92-AS1 may affect leukocytes via regulation of the expression of granulocyte colony-stimulating factor in GC tissues. Our data provide an in-depth insight into the mechanism behind the lncRNA TMEM92-AS1, how it promotes GC progression and the possible mechanism in affecting peripheral leukocyte counts. Therefore, TMEM92-AS1 is a potential target for GC individualized therapy and prognostic assessment.

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.

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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.

[Clinical significance of prognostic nutritional index in patients with advanced gastric cancer].

OBJECTIVE: To investigate the relationship of prognostic nutritional index (PNI) with clinicopathological factors and the clinical significance of PNI in predicting the survival in patients with advanced gastric cancer. METHODS: Clinicopathological and follow-up data of 1150 patients with advanced gastric cancer who underwent radical gastrectomy from January 2007 to December 2010 at the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital were analyzed retrospectively. The PNI value was calculated [PNI=absolute value of lymphocyte(109/L)×5 + serum albumin (g/L)] and was grouped according to the mean value of PNI. Relationships of PNI with gender, age, tumor size, depth of invasion, tumor differentiation, tumor stage, tumor location, lymph node metastasis and tumor marker detection level were analyzed. At the same time, for the survival analysis of patients, log-rank method was used for univariate analysis, and Cox method was used for multivariate analysis. RESULTS: Of 1150 cases, 846 were males and 304 were females with an average age of 62 (24 to 88) years. The average maximum diameter of tumor was 5.4(1.0 to 20.0) cm. Tumor of 159 cases located in the gastric fundus, 221 cases in the gastric body, 705 cases in the gastric antrum and 65 cases in the whole stomach. Well differentiated tumors were found in 198 cases and poorly differentiated tumors in 952 cases. As for depth of tumor invasion, 165 cases were T2, 343 cases were T3 and 642 cases were T4. According to TNM stage, 53 cases were stage I(, 397 cases were stage II( and 700 cases were stage III(. The average lymph node metastasis rate was 25.0%, meanwhile lymph node metastasis was N0 in 296 cases, N1 in 246 cases, N2 in 277 cases and N3 in 331 cases. Blood examination showed hemoglobin ≤130 g/L in 544 cases and >130 g/L in 606 cases; carcinoembryonic antigen ≤5 µg/L in 903 cases and >5 µg /L in 247 cases; carbohydrate antigen 19-9 ≤37 kU/L in 927 cases and >37 kU/L in 223 cases. In whole patients, the mean value of PNI was 51.81(24.5 to 80.4), PNI ≤51.81 group had 563 cases, and PNI >51.81 group had 587 cases. Between PNI ≤51.81 group and PNI >51.81 group, age (χ2=22.661, P=0.000), tumor location (χ2=8.979, P=0.030), tumor size (χ2=34.509, P=0.000), tumor stage (χ2=11.644, P=0.003), depth of tumor invasion (χ2=21.681, P=0.000) and hemoglobin (χ2=112.262, P=0.000) were significantly different. Patients were followed up for an average of 45.1 months (4 to 108). The 5-year survival rate was 37.7% in PNI ≤51.81 group, while it was 47.0% in PNI >51.81 group, whose difference was statistically significant (χ2=8.326, P=0.004). Univariate analysis showed that patients with PNI ≤51.81(P=0.004), deeper tumor invasion (P=0.000), more metastatic lymph nodes (P=0.000), later TNM stage (P=0.000), lymph node metastasis rate >25.02%(P=0.000), hemoglobin ≤130 g/L(P=0.011), the maximum tumor diameter >5.4 cm (P=0.000), tumor undifferentiated (P=0.001), CEA >5 µg /L (P=0.000), CA199 >37 kU/L(P=0.000) and tumors locating in whole stomach (P=0.000) had poorer prognosis. Multivariate analysis showed that the age (HR=1.195, 95%CI: 1.019 to 1.401, P=0.028), the depth of tumor invasion(HR=1.429, 95%CI: 1.231 to 1.658, P=0.000), the number of metastatic lymph node (HR=1.536, 95%CI:1.330 to 1.774, P=0.000), the lymph node metastasis rate (HR=1.376, 95%CI:1.102 to 1.717, P=0.005), tumor TNM stage (HR=1.387, 95%CI: 1.026 to 1.876, P=0.033) and tumor size(HR=1.182, 95%CI: 1.005 to 1.390, P=0.043) were independent prognostic factors of gastric cancer patients, while PNI (HR=0.913, 95%CI: 0.774 to 1.076, P=0.278) was not an independent risk prognostic factor of gastric cancer patients. CONCLUSIONS: Although the PNI is not an independent risk factor of overall survival in patients with advanced gastric cancer, it is still an indicator of survival in patients with gastric cancer. Improving preoperative nutritional status in patients with gastric cancer may contribute to a better prognosis.

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.

Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be better biomarkers for predicting overall survival of patients with advanced gastric cancer.

BACKGROUND AND OBJECTIVES: Preoperative systemic inflammatory response and nutritional status play important roles in the tumorigenesis, progression, and prognosis of gastric cancer (GC). This research is designed to investigate the prognostic value of the biomarkers including the neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) in predicting overall survival in patients with GC. METHODS: A total of 1,990 consecutive GC patients who underwent gastrectomy from 2007 to 2011 were enrolled and divided into high level and low level based on the optimal cut-off points for NLR, dNLR, MLR, PLR, and PNI, respectively. The clinicopathological characteristics of the two levels were comparatively analyzed. Overall survival analysis was executed using these biomarkers and clinicopathological characteristics. RESULTS: The number of metastatic lymph nodes, distant metastasis, American Joint Committee on Cancer TNM stage, radicality, tumor size, metastatic lymph nodes ratio, ascites, and Hb were all significantly associated with NLR, dNLR, MLR, PLR, and PNI. All of these five biomarkers were closely associated with overall survival in univariate analyses, but only dNLR and MLR were significant in multivariate model. dNLR and MLR can be bonded to predict survival, but whether separate or together, dNLR and MLR were mainly significant in advanced stages. CONCLUSION: Although preoperative NLR, dNLR, MLR, PLR, and PNI in peripheral blood proved significant prediction of prognoses of postoperative GC patients, dNLR and MLR may be better biomarkers for predicting overall survival, especially in advanced GC patients.

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.

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.

Systemic Inflammation Response Index (SIRI), cancer stem cells and survival of localised gastric adenocarcinoma after curative resection.

PURPOSE: Systemic Inflammation Response Index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently developed and used as a marker to predict the survival of patients with malignant tumours. Cancer stem cells (CSCs) can contribute to gastric cancer progression and recurrence. It is not clear whether SIRI is associated with CSCs during gastric cancer development. METHODS: The SIRI was developed in a training cohort of 455 gastric cancer patients undergoing curative resection between 2007 and 2009, and validated in a validation cohort of 327 patients from 2010 to 2011. CD44 + CSCs were measured on tumour sections by immunohistochemical analysis. RESULTS: An optimal cut-off point for the SIRI of 0.82 divided the gastric cancer patients into a low SIRI group (SIRI < 0.82) and a high SIRI group (SIRI ≥ 0.82) in the training cohort. Compared with patients who had a SIRI < 0.82, patients who had a SIRI ≥ 0.82 had a shorter disease-free survival (DFS) (HR 2.529; 95% CI 1.922-3.326; p < 0.001) and shorter disease-special survival (DSS) (HR 2.692; 95% CI 2.022-3.585; p < 0.001) in the training cohort, comparable DFS and DSS findings were observed in the validation cohort, even for patients in pathological TNM stage of I subgroup. A SIRI ≥ 0.82 was significantly associated with older age, larger tumour, higher pathological TNM stage, lymphovascular invasion, and perineural invasion. Additionally, patients in the low SIRI group were prone to DFS and DSS benefits from postoperative adjuvant chemotherapy. Univariate and multivariate analyses revealed that SIRI was an independent predictor for DFS and DSS. Furthermore, gastric cancer patients with CD44 + CSCs scores had higher SIRI level (mean 1.198 vs. 0.835; p < 0.001). In patients with CD44 + CSCs, those with SIRI ≥ 0.82 had higher recurrence rates and shorter survival time than patients with SIRI < 0. 82. CONCLUSIONS: SIRI was a useful prognostic indicator of poor outcomes in patients with gastric cancer and is a promising tool for gastric cancer treatment strategy decisions. The dismal outcomes in patients with high SIRI might be related to CSCs.

[Clinicopathological factor analysis of positive cells in peritoneal lavage of gastric carcinoma].

OBJECTIVE: To explore the clinicopathological factors affecting positive cells in peritoneal lavage of gastric carcinoma. METHODS: Clinicopathological data of 163 patients undergoing radical operation for gastric carcinoma and receiving cytology examination of peritoneal lavage (1000 ml normal saline) in our department from June 2013 to May 2014 were analyzed retrospectively. Pathology and immunohistochemistry were performed for resected lesions and harvested lymph nodes. Affecting factors of peritoneal lavage cytology were evaluated with univariate and multivariate logistic analyses. RESULTS: The positive rate of exfoliative carcinoma cells was 9.2%(15/163). Univariate analysis showed that pathologic staging, depth of invasion, N staging, lymph node metastasis, station of positive lymph node, metastatic rate of lymph node, metastatic rate of the second station of lymph node, and carcinoma differentiation degree were associated with the positive rate of peritoneal lavage cytology (all P<0.05). Multivariate analysis revealed only the metastatic rate of the second station of lymph node was independent risk factor of positive exfoliative cells in peritoneal lavage. CONCLUSION: The metastatic rate of the second station of lymph node is an independent risk factor of positive exfoliative cells in peritoneal lavage for gastric cancer patients.