Prognostic Factor In Gastric Cancer Research Articles

HER2 Oncogene Amplification and Immunohistochemical Profiling in Gastric Adenocarcinoma.

Background and Objectives: Gastric adenocarcinoma is one of the most common malignant tumors and a major cause of cancer death worldwide, especially in developing countries. Her2/neu gene amplification and protein overexpression in breast cancer is a golden criterion for the targeted therapy with trastuzumab. However, the role of Her2 as a prognostic factor in gastric cancer is still controversial. The purpose of this study was to evaluate the frequency of Her2 oncogene overexpression and concordance between the results for Her2 protein expression and gene amplification. Materials and Methods: A total of 65 retroprospective cases with gastric adenocarcinoma, including biopsy and resected specimens obtained between July 2015 to December 2017, were analyzed. Her2/neu expression was determined by Immuno-histochemistry (IHC). Equivocal and some selected cases were submitted for FISH to detect Her2/neu gene amplification. Results: In the present study, out of 65 patients of gastric adenocarcinoma, there were 50 males and 15 females, with mean age of 54.52 years. The majority of tumors were located within the antropyloric region. We found 27 (41.4%) positivity, scored as IHC 3+ and IHC 2+, and 38 (58.3%) negativity, scored as IHC 1+ and IHC 0. We also evidentiated a significant difference between Her2/neu expression with age (p=0.010) and depth of invasion (p=0.020).Her2/neu gene was amplified only in 13 cases, 4 cases were of Her2/neu (3+) positive, 11 cases (39.3%) Her2/neu (2+) with IHC staining. The concordance rate between the results of IHC and FISH in all 18 cases was 83.3%. Conclusion: IHC detection can be carried out to guide the treatment when FISH detection cannot be performed. Overexpression of Her 2/neu in gastric adenocarcinoma could potentially be used in selecting the patients who can get benefit from the anti-Her2/neu targeted therapy.

Comprehensive bioinformatics analysis of lncRNAs in gastric cancer.

Long non-coding RNAs (lncRNAs) have been generally considered to serve important roles in various types of cancer, including gastric cancer. However, a comprehensive understanding of lncRNAs in gastric cancer requires further study. The present study performed an in-depth study revealed 50 differently expressed lncRNAs. The changed cellular pathways and biological process in gastric cancer were determined. To further confirm the functions of the differently expressed lncRNAs, co-expression networks were constructed between the lncRNAs and mRNA; this lead to the identification of 6 modules, which participated in various cellular pathways. In addition, 2 lncRNAs were identified which were associated with clinical outcome. The biological analysis and experimental evidence suggested that LINC00982 inhibited, while LL22NC03-N14H11.1 promoted the proliferation of gastric cancer cells. These lncRNAs may be considered as potential prognostic factor in gastric cancer.

The prognostic value of a Surgical Outcome Risk Tool in patients after radical gastrectomy for gastric cancer and its guiding significance for postoperative chemotherapy

ObjectiveTo provide individualized survival predictors for patients after radical gastrectomy and to guide adjuvant treatment. MethodsThe data of patients with gastric cancer treated in our department from January 1996 to December 2014 were analyzed retrospectively. A Surgical Outcome Risk Tool (SORT) was used to indicate the physical condition of the patients. ResultsA total of 5327 patients in the study. The 5-year overall survival rates in the low-, moderate- and high-risk group were 61.6%, 54.7% and 44.4%, respectively (p < 0.001). A multivariate analysis showed that SORT was an independent prognostic factor for gastric cancer. There was significant chemotherapy benefit after surgery in stage II-III patients with a SORT<3 and in stage III patients with a SORT≥3 (p < 0.05). However, chemotherapy did not improve the 5-year overall survival in stage II patients with a SORT≥3 (62.4% vs. 48.3%, p = 0.196). The calculated difference between two nomogram models was the potential benefit of adjuvant chemotherapy for patients with gastric cancer. ConclusionA SORT is an independent risk factor for predicting the prognosis of gastric cancer, and postoperative adjuvant chemotherapy should be carefully adopted in stage II patients with a SORT≥3.

HAVCR1 expression might be a novel prognostic factor for gastric cancer.

Hepatitis A virus cellular receptor 1 (HAVCR1), which is also known as T-cell immunoglobulin and mucin domain 1 (TIM-1) is a TIM gene family member. In this study, we aimed to characterize the expression profile of HAVCR1 in GC, its prognostic value and the potential epigenetic mechanism leading to its dysregulation. Bioinformatic analysis was performed by using genomic, clinicopathological and survival data in the human protein atlas (HPA) and the Cancer Genome Atlas (TCGA). Results showed that HAVCR1 was significantly upregulated at the mRNA and protein level in GC tissues compared to the adjacent normal tissues. In addition, HAVCR1 upregulation was an independent indicator of shorter OS (HR: 1.698, 95%CI: 1.221–2.361, p = 0.002), after adjustment of older age, differentiation status, pathological stages and the presence of residual tumor and was also an independent indicator of shorter RFS (HR: 2.577, 95%CI: 1.583–4.197, p<0.001), after adjustment of gender and histological grade. The methylation level of two CpG sites (cg11188031 and cg07320595) was negatively correlated with HAVCR1 expression. However, only high methylation level of cg07320595 was associated with significantly longer OS (p = 0.018) and RFS (p = 0.021). Based on these findings, we infer that HAVCR1 upregulation might serve as a valuable prognostic marker in terms of OS and RFS in GC patients. Cg07320595 might be a critical CpG site influencing HAVCR1 expression.

The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer

ABSTRACTObjective: Angiogenesis is one of the key processes in the development of malignant tumors. The vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) signaling pathway regulates branching angiogenesis in cancer. In this study, we analyzed the associations of VEGF/VEGFR-2 proteins and VEGFR-2 genetic variations with the prognosis of gastric cancer (GC).Method: We collected the clinical information of patients with GC and extracted genomic DNA from paraffin-embedded tissues. Immunohistochemical methods were used to detect the expression of VEGF and VEGFR-2 in GC tissues. Four single nucleotide polymorphisms of VEGFR-2 were detected by the TaqMan assay. The Kaplan-Meier method and Cox regression model were applied to analyze the associations between clinicopathological characteristics, VEGFR-2 polymorphisms and GC prognosis.Results: A total of 256 cases of GC were included in our study. VEGFR-2 (+) and VEGFR-2 (++/+++) protein expression levels were detected in 83 and 135 cases, respectively. High expression of the VEGFR-2 protein was associated with the poor prognosis of GC (log-rank test P = 0.026). No statistical significance was observed for the association between VEGF and the prognosis of GC. The VEGFR-2 rs1870377 A > T genetic polymorphism was discovered to be associated with the prognosis of GC (AA vs. AT, HR = 1.69, 95% CI = 1.06–2.68, P = 0.027).Conclusion: Our study suggested that the high expression of VEGFR-2, as well as the VEGFR-2 rs1870377 A > T genetic polymorphism, may be prognostic markers for GC.

Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer

ObjectiveTo explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. MethodsThe Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan–Meier survival curve analysis. ResultsAfter filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). ConclusionsNF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

Survival Outcomes and Prognostic Factors for Gastric Cancer in the Adjuvant Setting: An Analysis of the National Cancer Database

Survival Outcomes and Prognostic Factors for Gastric Cancer in the Adjuvant Setting: An Analysis of the National Cancer Database

Re-emerging role of macroscopic appearance in treatment strategy for gastric cancer.

Pathological outcomes are definitely the most important prognostic factors in gastric cancer, but they can be obtained only after surgical resection. Use of preoperative adjuvant chemotherapy is becoming widespread for aggressive human cancer, so clinical factors such as macroscopic features are important as they are highly predictive for patient prognosis. In gastric cancer, the macroscopic type represents a distinct prognosis; Type 0 represents early gastric cancer with excellent prognosis, but, among advanced tumors, giant Type III and Type IV tumors have a dismal prognosis. Japan Clinical Oncology Group (JCOG) Stomach Cancer Study Group adopted macroscopic features as high‐risk entities in clinical trials. It makes sense for risk classification to use macroscopic phenotypes because The Cancer Genome Atlas (TCGA) Network has lately subcategorized different histologies associated with specific macroscopic types by the molecular features of the whole genome. Dismal prognosis of Type IV gastric cancer is notorious, but similar prognosis was seen in giant Type III gastric cancer defined as 8 cm or beyond, both of which are unique for their propensity of peritoneal dissemination. In this review, clinical relevance including prognosis of such macroscopic high‐risk features will be separately debated in the context of precision medicine and updated prognostic outcomes will be presented under the present standard therapy of curative surgery followed by postoperative S‐1 chemotherapy. Moreover, promising emerging novel therapeutic strategies including trimodal potent regimens or intraperitoneal chemotherapy will be described for such aggressive gastric cancer.

MiR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1.

Chemotherapy is an important treatment option for gastric cancer (GC); however, chemotherapy usually fails due to drug resistance, particularly multidrug resistance (MDR). In our previous studies, microRNA (miR)‑874 was demonstrated to serve an important role in tumour growth, apoptosis and angiogenesis. In the present study, the precise roles and underlying mechanisms of miR‑874 in MDR were investigated in GC. The overexpression of miR‑874 reversed cancer cell drug resistance invitro. According to reporter gene and western blot assays, Autophagy‑related16‑like1(ATG16L1) was identified as a direct target of miR‑874. ATG16L1 was also demonstrated to be positively associated with autophagy. Reducing the expression of ATG16L1 and inhibiting the occurrence of autophagy sensitized GC cells to chemotherapy. Thus, the miR‑874/ATG16L1/autophagy regulatory loop was demonstrated to serve an important role in MDR in GC. Furthermore, miR‑874 may be used as a prognostic factor in GC. Overall, miR‑874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1, highlighting the potential clinical application of miR‑874 in chemotherapeutic resistance.

Neutrophil-to-lymphocyte ratio as a predictive or prognostic factor for gastric cancer treated with nivolumab: a multicenter retrospective study.

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) is effective as a predictive factor for lung cancer treated with nivolumab. The objective of this study was to determine the effectiveness of NLR for patients with advanced gastric cancer (AGC) treated with nivolumab.MethodsThis was a multicenter, retrospective study of patients with AGC treated with nivolumab from June 2017 to December 2017. The NLRs were calculated before the first cycle (NLRpre) and two weeks after the first administration (NLRpost).ResultsTwenty-six patients were enrolled (males 19, females 7) with a median age of 64 years. The overall response rate was 15%. The median PFS was 80 days (range, 11 – 265) and the median OS was 290 days (range, 21 – 332). Stratified with high NLR (≥5) and low NLR (<5), the median PFS was shorter in the high NLRpre arm (87 vs. 45 days; p=0.066) and significantly shorter in the high NLRpost arm (94 vs. 28 days; p=0.014). The median OS was significantly shorter in the high NLRpre arm (290 vs. 175 days; p=0.008) and in the high NLRpost arm (290 vs. 69 days; p<0.001).ConclusionNLR may be an effective prognostic factor in patients with AGC treated with nivolumab.

Low expression of CDK5RAP3 and DDRGK1 indicates a poor prognosis in patients with gastric cancer

AIMTo investigate the effects of different levels of expression of CDK5RAP3 and DDRGK1 on long-term survival of patients undergoing radical gastrectomy.METHODSThe expression of CDK5RAP3 and DDRGK1 was detected by immunohistochemistry in 135 patients who received standard gastrectomy were enrolled in the study. Western Blot was used to detect the expression of CDK5RAP3 and DDRGK1 in gastric cancer and its adjacent tissues and cell lines. The correlations between the expression of CDK5RAP3 and DDRGK1 and clinicopathological factors were analyzed, and the value of each parameter to the prognosis of the patients was compared. Receiver operating characteristic analysis was used to compare the accuracy of the prediction of clinical outcome by the parameters.RESULTSCDK5RAP3 and DDRGK1 expression was down-regulated in the gastric cancer compared to its respective adjacent non-tumor tissues. The expression of CDK5RAP3 was closely related to the age of the patients (P = 0.035) and the T stage of the tumor (P = 0.017). The expression of DDRGK1 was correlated with the sex of the patients (P = 0.080), the degree of tumor differentiation (P = 0.036), the histological type (P = 0.036) and the N stage of the tumor (P = 0.014). Low expression CDK5RAP3 or DDRGK1 is a poor prognostic factor for gastric cancer patients. Prognostic analysis showed that the co-expression of CDK5RAP3 and DDRGK1 was an independent prognostic factor correlating with the overall survival of gastric cancer patients. Combined expression analysis of CDK5RAP3 and DDRGK1 may provide a more accurate prognostic value for overall survival.CONCLUSIONThe co-expression of CDK5RAP3 and DDRGK1 is an independent prognostic factor for gastric cancer, which can provide a more accurate model for the long-term prognosis.

Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review

Gastric adenocarcinoma is one of the most common types of cancer worldwide, with an incidence of a million new cases annually. In addition to having a high mortality rate due to often delayed detection and its poor response to cancer therapy, it also spreads aggressively. Inflammation has been shown to play a role in carcinogenesis. Consequently, macrophages are important in phagocytosis, antigen presenting and producing cytokines and growth factors. As a response to microenvironmental signals, they may polarize into tumor resisting M1 or tumor promoting M2 macrophages. Recently, studies have indicated that M2-type macrophage resembling tumor-associated macrophages (TAMs) might be used as an independent prognostic factor for gastric cancer. This review will discuss the possible use of TAMs as prognostic tools for gastric cancer and whether they are suitable for use in clinical environment.

Prognostic factors for cytology-positive gastric cancer

Positive peritoneal lavage cytology for gastric carcinoma cells (CY1) is considered distant metastasis and is classified as Stage IV. However, patients with CY1 comprise a heterogeneous population, and their prognosis varies greatly. The prognostic factors for gastric cancer patients with CY1 were retrospectively reviewed. The participants were 80 gastric cancer patients with CY1 in our institution encountered between 2005 and 2017. Prognostic factors were analyzed using univariate and multivariate analyses. The operative procedure was distal gastrectomy for 30 patients, total gastrectomy for 27 patients, staging laparoscopy for 10 patients, gastrojejunostomy for 8 patients, and probe laparotomy for 5 patients. Other distant metastases were recognized in 36 patients. A multivariate analysis revealed that other distant metastases were the strongest independent risk factor for the overall survival (p < 0.0001). When the cohort was limited to CY1 patients without other distant metastases, cN2-3 (p = 0.01), the prognostic nutritional index (PNI) < 40 (p = 0.02) and Type 4 (p = 0.03) were independent risk factors according to a multivariate analysis. The survivals of patients with cN2-3 or PNI < 40 after gastrectomy were equivalent to those with other distant metastases, as assessed by log-rank analyses. The prognoses of CY1 gastric cancer patients with cN2-3 or PNI < 40 were poor, even after gastrectomy.

PTEN lipid phosphatase inactivation links the hippo and PI3K/Akt pathways to induce gastric tumorigenesis

BackgroundPhosphatase and tensin homolog (PTEN) is an important tumor suppressor gene, and its encoded protein has activities of both a protein phosphatase and a lipid phosphatase. However, the substitution effect of protein phosphatase activity remains unclear. PI3K/Akt is the most common pathway negatively regulated by PTEN. The Hippo and PI3K/Akt pathways have a joint effect in regulating cell proliferation and apoptosis. Therefore, how PTEN lipid phosphatase inactivation contributes to the occurrence and development of gastric cancer and the potential role of the Hippo and PI3K/Akt pathways in PTEN lipid phosphatase inactivation mediated gastric tumorigenesis remain to be explored.MethodsImmunohistochemical staining was performed to detect the expression of p-PTEN and YAP in a gastric cancer tissue microarray. Stable cell lines expressing a wild-type or dominant-negative mutant PTEN were established. The proliferation and migration of stable cells were detected by MTT, BrdU, and colony-formation, transwell assay and high content analysis in vitro, and tumor growth differences were observed in xenograft nude mice. Changes in the expression of key molecules in the Hippo and Akt signaling pathways were detected by western blot. Nuclear-cytoplasm separation, immunofluorescence and coimmunoprecipitation analyses were conducted to explore the dysregulation of Hippo in the stable cell lines.ResultsPTEN lipid phosphatase inactivation strongly promoted the proliferation and migration of gastric cancer cells in vitro and tumor growth in vivo. A immunohistochemical analysis of gastric cancer tissues revealed a significant correlation between phosphorylated PTEN and nuclear YAP expression, and both were determined to be independent prognostic factors for gastric cancer. Mechanistically, PTEN lipid phosphatase inactivation abolished the MOB1-LATS1/2 interaction, decreased YAP phosphorylation and finally promoted YAP nuclear translocation, which enhanced the synergistic effect of YAP-TEAD, thus inducing cell proliferation and migration. Moreover, PTEN lipid phosphatase inactivation promoted the PI3K/Akt pathway, and disruption of YAP-TEAD-driven transcription decreased the activation of Akt in a dose-dependent manner.ConclusionsTaken together, our findings indicate that PTEN lipid phosphatase inactivation links the Hippo and PI3K/Akt pathways to promote gastric tumorigenesis and cancer development.

High miR-718 Suppresses Phosphatase and Tensin Homolog (PTEN) Expression and Correlates to Unfavorable Prognosis in Gastric Cancer.

BackgroundPhosphatase and tensin homolog (PTEN) is a kind of phosphatase which has been demonstrated to suppress progression of gastric cancer. Many micro-RNAs (miRNAs), such as miR-106b, miR-93, and miR-200c, could inhibit expression of PTEN in cell lines; and many miRNAs including miR-21, miR-22, miR-18a, and miR-222 are related to the progression and prognosis of gastric cancer. However, among these miRNAs, the clinical significance of miR-718 has not yet been elucidated.Material/MethodsThe expression of PTEN and miR-718 in 141 gastric cancer tissues were detected by immunohistochemistry and quantitative real-time PCR respectively. The correlation between PTEN, miR-718, and the clinicopathological factors was analyzed by χ2 test. The prognostic significance of PTEN and miR-718 was evaluated by univariate and multivariate analysis. Luciferase reporter assay was performed to evaluate the regulation of PTEN by miR-718. The effect of miR-718 on gastric cancer proliferation and invasion was investigated by MTT assay and Transwell assay.ResultsLow expression of PTEN and high expression of miR-718 were both significantly associated with unfavorable prognosis, and both were identified as biomarkers predicting poorer prognosis of patients with gastric cancer. Increased miR-718 expression could decrease PTEN expression, thus enhancing phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt) signaling. Moreover, the abilities of proliferation and invasion of gastric cells transfected with miR-718 were promoted significantly compared with those transfected with control miRNA.ConclusionsLow expression of PTEN and increased expression of miR-718 in gastric cancer tissues were both independent unfavorable prognostic factors of gastric cancer. Upregulation of miR-718 could increase PI3K/Akt signaling by directly downregulating PTEN, thus promoting the proliferation and invasion of gastric cancer cells.

Gene regulatory network construction identified NFYA as a diffuse subtype-specific prognostic factor in gastric cancer.

Lauren classification is a pathology-based gastric cancer (GC) subtyping system, which is widely used in the clinical treatment of patients with GC. However, genome- scale molecular characteristics to distinguish between diffuse (DF) and intestinal (IT) GC remain incompletely characterized, particularly at the transcriptional regulatory level. In the present study, gene regulatory networks were constructed using the Passing Attributes between Networks for Data Assimilation (PANDA) algorithm for DF, IT and mixed GC. The results indicated that >85% of transcription factor (TF)-target edges were shared among all three GC subtypes. In TF enrichment analysis, 13 TFs, including nuclear transcription factor Y subunit α (NFYA) and forkhead box L1, were activated in DF GC, whereas 8 TFs, including RELA proto-oncogene and T-cell leukemia homeobox 1 (TLX1), were activated in IT GC. Out of these identified TFs, NFYA [Hazard ratio (HR) (95% confidence interval, CI)=0.560 (0.349, 0.900), P=0.017] and sex determining region Y [HR (95% CI)=0.603 (0.375, 0.969), P=0.037] were identified as independent prognostic factors in DF GC, but not in IT GC, whereas TLX1 [HR (95% CI)=0.547 (0.321, 0.9325), P=0.027] was identified as an independent prognostic factor in IT GC, but not in DF GC. Verification at the cellular level was also performed; interference of NFYA expression using small interfering RNA in MGC803 cells (DF GC-derived cells) markedly inhibited cell growth and colony formation. Similar effects were also detected in SGC-7901 cells (IT GC-derived cells), but to a lesser extent. In conclusion, identified gene regulatory networks differed between distinct GC subtypes, in which the same TFs had different biological effects. Specifically, NFYA was identified as a DF subtype- specific independent prognostic factor in GC.

Relationship between PD-L1 protein expression and gene amplification in gastric cancer tissues

Objective: To investigate the relationship of PD-L1 protein expression and gene amplification in gastric cancer and their correlation with clinicopathologic factors. Methods: The cohort included 247 gastric cancer specimens with follow-up data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD-L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: PD-L1 protein was expressed in 25.9% (64/247) of the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC). There was a correlation between the two (P<0.01). The expression of PD-L1 in tumor cells correlated with the degree of differentiation and tumor diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0% (47/247), and was associated with age, large/small curvature of the stomach, tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting that the coincidence of IHC and FISH was poor (P=0.157). There was a negative correlation between PD-L1 protein expression on tumor cells and prognosis in gastric cancer. There was no significant correlation between PD-L1 protein expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression analysis showed that PD-L1 protein expression, depth of invasion and lymph node metastasis were all independent prognostic risk factors for gastric cancer. Conclusions: Concordance between PD-L1 protein expression and gene amplification is poor. PD-L1 protein expression may signify poor prognosis. There is no significant correlation between PD-L1 gene amplification and prognosis of patients with gastric cancer.

High serum Ephrin-B2 levels predict poor prognosis for patients with gastric cancer.

Gastric cancer is an intractable disease with a poor prognosis and limited treatment options. Its treatment remains a major clinical challenge worldwide. Ephrin-B2 is upregulated and involved in tumor growth in various types of cancer. However, the association between ephrin-B2 and prognosis of gastric cancer, and the potential of ephrin-B2 as a therapeutic target remains unknown. The present study investigated ephrin-B2 as a prognostic factor and a therapeutic target for gastric cancer. Reverse transcription-quantitative polymerase chain reaction was performed to detect the protein expression level of ephrin-B2 in gastric cancer serum samples (n=162) and healthy serum samples (n=165). It was revealed that the protein expression level of ephrin-B2 was significantly upregulated in gastric cancer serum samples compared with the healthy samples. Ephrin-B2 protein expression was associated with tumor size (P<0.001), metastasis (P=0.02) and TNM stage (P=0.03), and was indicated to be an independent prognostic factor for gastric cancer. Furthermore, the Kaplan-Meier survival curve demonstrated that patients with high ephrin-B2 protein expression had shorter overall and progression-free survival rates than those with low ephrin-B2 protein expression. Ephrin-B2 protein expression was induced by small interfering RNA (siRNA) transfection of HGC27 and MKN-45 cells, significantly impeding cell viability and inducing apoptosis of HGC27 and MKN-45 cells compared with the respective negative control (NC) group. Thus, to the best of our knowledge, the present study indicates that ephrin-B2 functions as an oncogene in gastric cancer, and that serum ephrin-B2 level may be a promising non-invasive prognostic indicator, as well as a therapeutic target for gastric cancer.

Distinct subgroup of the Ras family member 3 (DIRAS3) expression impairs metastasis and induces autophagy of gastric cancer cells in mice

PurposeDistinct subgroup of the Ras family member 3 (DIRAS3), also called Aplasia Ras homolog member I, is a tumor suppressor gene that induces autophagy in several cancer cell lines.MethodsThis study analyzed DIRAS3, and markers of autophagy (p62, and LC3B-II) in surgically resected GC samples from 420 patients. The promotion of autophagy by DIRAS3 in gastric cancer (GC) cells was explored, which might explain its inhibitory role in gastric cancer cells.ResultsDIRAS3 expression in GC was positively correlated with LC3B-II amount, and negatively with metastasis; DIRAS3 and p62 levels were independent prognostic factors in GC. Overexpression of DIRAS3 in BGC-823 cells induced autophagy, led to decreased proliferation, cell cycle arrest in G0/G1 phase, increased apoptosis, and impaired migration and invasion. While knockdown of DIRAS3 promoted proliferation and migration in MKN-45 cells. Overexpression of DIRAS3 in BGC-823 cells elevated autophagy levels in subcutaneous xenograft and inhibited tumor growth in mice; the hematogenous liver and lung metastasis of cancer cells were also suppressed.ConclusionsIn conclusion, the results suggest DIRAS3 may play a role in affecting proliferation and metastatic potential of GC cells, which may be associated with its involvement in autophagy regulation.

Prognostic analysis of stage III gastric cancer after curative surgery according to the newest TNM classification.

To study the prognostic factors of gastric cancer (GC) patients who were classified with stage III disease according to the newest TNM classification. This study retrospectively enrolled 279 patients who underwent radical gastrectomy from January 2012 to December 2014 at our hospital and who were diagnosed with stage III GC according to the new 8th edition of the TNM classification. The patient data that were collected included age, sex, pathological parameters, survival, lymph node ratio, neo-adjuvant chemotherapy with oxaliplatin and S-1, and operation type. The characteristics, survival, and prognostic factors of the patients were analyzed by univariate and multivariate analyses. The median OS of the patients after curative surgery was 19months, and the 3-year survival rate (3-YSR) was 25.3%. A univariate analysis showed that tumor location (P = 0.01), neo-adjuvant chemotherapy (P = 0.005), pathological T stage (P = 0.002), pathological N stage (P < 0.001), lymph node ratio (LNR) (P < 0.001), and operation type (P = 0.032) were significantly associated with overall survival. A multivariate analysis revealed that neo-adjuvant chemotherapy (P = 0.009), pathological T stage (P = 0.012), and LNR (P < 0.001) were independent prognostic factors. Neo-adjuvant chemotherapy, pathological T stage, and LNR were independent prognostic factors for the overall survival of patients with stage III GC. The neo-adjuvant chemotherapy with oxaliplatin and S-1 can be used for the patients to improve their survival.