Evolutionary and immune-activating character analyses of NLR genes in algae suggest the ancient origin of plant intracellular immune receptors.

Nucleotide-binding leucine-rich repeat (NLR) proteins are crucial intracellular immune receptors in plants, responsible for detecting invading pathogens and initiating defense responses. While previous studies on the evolution and function of NLR genes were mainly limited to land plants, the evolutionary trajectory and immune-activating character of NLR genes in algae remain less explored. In this study, genome-wide NLR gene analysis was conducted on 44 chlorophyte species across seven classes and seven charophyte species across five classes. A few but variable number of NLR genes, ranging from one to 20, were identified in five chlorophytes and three charophytes, whereas no NLR gene was identified from the remaining algal genomes. Compared with land plants, algal genomes possess fewer or usually no NLR genes, implying that the expansion of NLR genes in land plants can be attributed to their adaptation to the more complex terrestrial pathogen environments. Through phylogenetic analysis, domain composition analysis, and conserved motifs profiling of the NBS domain, we detected shared and lineage-specific features between NLR genes in algae and land plants, supporting the common origin and continuous evolution of green plant NLR genes. Immune-activation assays revealed that both TNL and RNL proteins from green algae can elicit hypersensitive responses in Nicotiana benthamiana, indicating the molecular basis for immune activation has emerged in the early evolutionary stage of different types of NLR proteins. In summary, the results from this study suggest that NLR proteins may have taken a role as intracellular immune receptors in the common ancestor of green plants.

The RNAome landscape of tomato during arbuscular mycorrhizal symbiosis reveals an evolving RNA layer symbiotic regulatory network.

Arbuscular mycorrhizal symbiosis (AMS) is an ancient plant-fungus relationship that is widely distributed in terrestrial plants. The formation of symbiotic structures and bidirectional nutrient exchange requires the regulation of numerous genes. However, the landscape of RNAome during plant AMS involving different types of regulatory RNA is poorly understood. In this study, a combinatorial strategy utilizing multiple sequencing approaches was used to decipher the landscape of RNAome in tomato, an emerging AMS model. The annotation of the tomato genome was improved by a multiple-platform sequencing strategy. A total of 3,174 protein-coding genes were upregulated during AMS, 42% of which were alternatively spliced. Comparative-transcriptome analysis revealed that genes from 24 orthogroups were consistently induced by AMS in eight phylogenetically distant angiosperms. Seven additional orthogroups were specifically induced by AMS in all surveyed dicot AMS host plants. However, these orthogroups were absent or not induced in monocots and/or non-AMS hosts, suggesting a continuously evolving AMS-responsive network in addition to a conserved core regulatory module. Additionally, we detected 587 lncRNAs, ten miRNAs, and 146 circRNAs that responded to AMS, which were incorporated to establish a tomato AMS-responsive, competing RNA-responsive endogenous RNA (ceRNA) network. Finally, a tomato symbiotic transcriptome database (TSTD, https://efg.nju.edu.cn/TSTD) was constructed to serve as a resource for deep deciphering of the AMS regulatory network. These results help elucidate the reconfiguration of the tomato RNAome during AMS and suggest a sophisticated and evolving RNA layer responsive network during AMS processes.

General Synthesis of Tube-like Nanostructured Perovskite Oxides with Tunable Transition Metal-Oxygen Covalency for Efficient Water Electrooxidation in Neutral Media.

Hydrogen production from water electrolysis in neutral-pH electrolytes can not only avoid the corrosion and safety issues and expand the catalyst option but also potentially integrate with artificial photosynthesis and bioelectrocatalysis. However, heterogeneous catalysts that can efficiently negotiate the sluggish oxygen evolution reaction (OER) in neutral solutions are considerably lacking. Herein, we report a template-assisted strategy for the synthesis of 13 kinds of tube-like nanostructured perovskite oxides (TNPOs) with markedly high Brunauer-Emmett-Teller surface areas. By systematic examination of these TNPOs, we found that the OER activity of TNPOs in neutral solution exhibits a volcano shape as a function of the covalency of transition metal-oxygen bonds. Consequently, our designed Sm-doped LaCoO3 catalyst yields a geometric current density of 8.5 mA cm-2 at 1.75 V versus the reversible hydrogen electrode in 1 M phosphate buffer solution (pH 7) due to the optimized covalency of Co 3d and O 2p states, representing the most active noble-metal-free OER catalyst in neutral electrolytes reported as yet.

Comparative Analysis of HSF Genes From Secale cereale and its Triticeae Relatives Reveal Ancient and Recent Gene Expansions.

Plants have evolved sophisticated systems to cope with the environmental stresses, with the heat shock factor (HSF) family proteins composing an integral part of the transcriptional regulation system. Understanding the evolutionary history and functional diversity of HSFs will facilitate improving tolerance of crops to adverse environmental conditions. In this study, genome-wide analysis of Secale cereale identified 31 HSF genes. The total number of HSF genes in S. cereale is larger than that in barley and the three subgenomes of wheat, suggesting it is a valuable resource for mining functional HSFs. Chromosome analysis revealed an uneven distribution of HSF genes among the 7 S. cereale chromosomes, with no HSF gene was detected on chromosome 4. Further interspecies synteny analysis revealed that chromosome reorganization during species-speciation may lead to the escape of HSF genes from the S. cereale chromosome 4. Phylogenetic analysis revealed that S. cereale experienced more HSF gene duplications than barley and the three wheat subgenomes. Expression analysis demonstrated that S. cereale HSF genes showed diverse expression patterns across plant developmental stages and upon drought and freezing treatment, suggesting functional diversity of the gene family. Notably, we detected distinct expression patterns for a recently duplicated HSF gene pair, indicating functional divergence may have occurred between the two genes. The study presents the genome organization, evolutionary features and expression patterns of the S. cereale HSF genes. These results provide new insights into the evolution of HSF genes in Triticeae and may serve as a resource for Triticeae molecular breeding.

Clean and Affordable Hydrogen Fuel from Alkaline Water Splitting: Past, Recent Progress, and Future Prospects.

Hydrogen economy has emerged as a very promising alternative to the current hydrocarbon economy, which involves the process of harvesting renewable energy to split water into hydrogen and oxygen and then further utilization of clean hydrogen fuel. The production of hydrogen by water electrolysis is an essential prerequisite of the hydrogen economy with zero carbon emission. Among various water electrolysis technologies, alkaline water splitting has been commercialized for more than 100 years, representing the most mature and economic technology. Here, the historic development of water electrolysis is overviewed, and several critical electrochemical parameters are discussed. After that, advanced nonprecious metal electrocatalysts that emerged recently for negotiating the alkaline oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are discussed, including transition metal oxides, (oxy)hydroxides, chalcogenides, phosphides, and nitrides for the OER, as well as transition metal alloys, chalcogenides, phosphides, and carbides for the HER. In this section, particular attention is paid to the catalyst synthesis, activity and stability challenges, performance improvement, and industry-relevant developments. Some recent works about scaled-up catalyst synthesis, novel electrode designs, and alkaline seawater electrolysis are also spotlighted. Finally, an outlook on future challenges and opportunities for alkaline water splitting is offered, and potential future directions are speculated.

Clinicopathological features and prognostic validity of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems in colonic neuroendocrine neoplasms.

PURPOSE: This study aimed to investigate the characteristics of colonic neuroendocrine neoplasms (NENs) and to validate the prognostic value of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems. METHODS: A total of 167 and 1248 patients with colonic NENs from 12 medical centers across China and from the Surveillance, Epidemiology, and End Results (SEER) cancer registry in the United States, respectively, were reviewed. Patients were staged according to the ENETS and AJCC 8th staging systems. RESULTS: Clinicopathological features of colonic NENs in the Chinese cohort and SEER cohort were significantly distinct. In both the Chinese cohort and the SEER cohort, colonic neuroendocrine carcinoma (NEC) and mixed adeno-neuroendocrine carcinoma (MANEC) were more frequent in the midgut than in the hindgut. Tumors originating from the midgut tended to be larger and at a more advanced stage than those from the hindgut. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC. CONCLUSIONS: Our study revealed that tumors originating from the midgut and the hindgut shared different clinicopathological features. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC.

Performance of risk stratification systems for gastrointestinal stromal tumors: A multicenter study.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor type in the gastrointestinal system. Presently, various classification systems to prognosticate GISTs have been proposed. AIM: To evaluate the application value of four different risk stratification systems for GISTs. METHODS: Patients who were diagnosed with GISTs and underwent surgical resection at four hospitals from 1998 to 2015 were identified from a database. Risk of recurrence was stratified by the modified National Institute of Health (NIH) criteria, the Armed Forces Institute of Pathology (AFIP) criteria, the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram, and the contour maps. Receiver operating characteristic (ROC) curves were established to compare the four abovementioned risk stratification systems based on the area under the curve (AUC). RESULTS: A total of 1303 patients were included in the study. The mean age of the patients was 55.77 ± 13.70 yr; 52.3% of the patients were male. The mean follow-up period was 64.91 ± 35.79 mo. Approximately 67.0% the tumors were located in the stomach, and 59.5% were smaller than 5 cm; 67.3% of the patients had a mitotic count ≤ 5/50 high-power fields (HPFs). Thirty-four tumors ruptured before and during surgery. Univariate analysis demonstrated that tumor size > 5 cm (P < 0.05), mitotic count > 5/50 HPFs (P < 0.05), non-gastric location (P < 0.05), and tumor rupture (P < 0.05) were significantly associated with increased recurrence rates. According to the ROC curve, the AFIP criteria showed the largest AUC (0.754). CONCLUSION: According to our data, the AFIP criteria were associated with a larger AUC than the NIH modified criteria, the MSKCC nomogram, and the contour maps, which might indicate that the AFIP criteria have better accuracy to support therapeutic decision-making for patients with GISTs.

Low expression of CD80 predicts for poor prognosis in patients with gastric adenocarcinoma.

AIM: To study the expression and prognostic significance of CD80 in patients with gastric adenocarcinoma. Materials & methods: Real-time quantitative PCR, western blot and immunohistochemistry were performed to detect the expression of CD80 in gastric cancer tissues and matched adjacent normal tissues. Double immunohistochemical staining was performed to preliminary examine the relationship between CD80+ cells and CD8+ cytotoxic T lymphocytes. RESULTS: The expression of CD80 was downregulated in tumor tissues compared with normal tissues (p = 0.002). Immunohistochemistry analysis showed that 49 (39.8%) of 123 patients with gastric cancer demonstrated reduced CD80 expression, which was correlated with the tumor differentiation grade. CONCLUSION: Our data suggest that reduced CD80 expression independently predicts a poor prognosis in patients with gastric adenocarcinoma.

A novel nomogram individually predicting disease-specific survival after D2 gastrectomy for advanced gastric cancer.

BACKGROUND: Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients. METHODS: A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat-sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell's C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets. RESULTS: The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.82 vs. 0.74; P < 0.001). In two validation sets, the nomogram's discrimination power was also excellent relative to TNM classification (C-index, 0.83 vs. 0.75 and 0.81 vs. 0.74, respectively; P < 0.001 for both). After calibration, the nomogram produced survival predictions that corresponded closely with actual survival rate. CONCLUSIONS: The established nomogram was able to predict 3-, 5-, and 10-year DSS probabilities for AGC patients. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity, suggesting its clinical utility.

AQP8 inhibits colorectal cancer growth and metastasis by down-regulating PI3K/AKT signaling and PCDH7 expression.

Colorectal cancer (CRC) is one of the most common malignant cancers and the leading cause of cancer-related deaths in worldwide. Although the monoclonal antibody therapy is prescribed for CRC, the metastasis resistant to therapy is the major cause of death of patients with CRC, which indicating the urgent demands for new therapeutic targets discovery. Aquaporin 8 (AQP8) has been identified alter expressed in several cancers including breast cancer, lung cancer and prostatic carcinoma. Our study demonstrated the functional significance of AQP8 in CRC cells growth and metastasis. Over-expression of AQP8 remarkably decreased growth, aggressiveness and colony formation in the CRC SW480 and HT-29 cells. Mechanistically, AQP8 over-expression inhibited tumorigenic phenotype by inactivating PI3K/AKT signaling and inhibiting PCDH7 expression. Furthermore, in vivo studies using nude mice xenograft and metastasis model identified the pivotal role of AQP8 in CRC cells growth and metastasis. Taken together, the present study verifies the vital role of the endogenous AQP8 in colorectal cancer progression.

Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy.

The role of palliative surgery is controversial in advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitors (TKIs) therapy.We evaluated safety and clinical outcomes in a single institution series of advanced GIST patients from January 2002 to December 2008.One hundred and fifty-six patients had been recruited, including 87 patients underwent surgical resection and 69 patients kept on TKIs treatment. Four patients had major surgical complications. Median follow-up was 38.3 months, the overall survival (OS) and progression-free survival (PFS) of the patients in surgical group were longer than the nonsurgical group, PFS: 46.1 versus 33.8 months (P < .01), OS: 54.8 versus 40.4 months. In the subgroup analysis for the patients received surgery, the median PFS for patients with progression disease, stable disease, and partial response was 33.3, 51.5, and 83.0 months, respectively (P < .01). Median OS was 68.0 months in those with only liver or peritoneal metastases, and 45.3 months in those with both metastases. Median PFS of patients underwent R0/R1 resection was 73.6 months compared with 35.8 months in R2 resection patients (P < .01).Patients with advanced GISTs have prolonged OS after debulking procedures. Surgery for patients who have responsive disease after TKIs treatment should be considered.

Surgical approach for Siewert type II adenocarcinoma of the esophagogastric junction: transthoracic or transabdominal? -a single-center retrospective study.

BACKGROUND: The surgical approach (transthoracic or transabdominal) for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) still remains controversial. METHODS: Data of patients with Siewert type II AEG were collected in the Guangdong General Hospital from 2004 to 2014 and we compared their clinicopathological outcome and prognosis in regard to the transthoracic (TT) and transabdominal (TA) approach. RESULTS: A total of 158 patients with Siewert type II AEG were analyzed and our results demonstrated that their overall medium survival was 52 months. Also, their 5-year overall survival rate was 39.1%, which was comparable between the TT and TA group (35.1% vs. 43.2%, P>0.05), while more lymph nodes were dissected in TA group (23.7±0.2 vs. 18.1±0.3, P<0.05), with less postoperative complications (14.3% vs. 28.4%, P<0.05) and shorten hospital stay (12±4 vs. 15±7 d, P<0.05). CONCLUSIONS: For patients with Siewert type II AEG, the TA approach is more suitable to achieve an optimal extent of lymph node dissection, reduction in the incidence of complication, shorten hospital stay, and to promote the recovery.

Time distribution of recurrence risk of oesophageal squamous cell carcinoma with complete resection (R0) in a Chinese population.

OBJECTIVES: We aimed to clarify the correlation between clinic-pathological characteristics and the distribution of recurrence probability during follow-up of oesophageal squamous cell carcinoma (OSCC) patients with complete resection analysis by hazard function, and to try to provide evidence-based data for optimal timing for adjuvant therapy. METHODS: A single-institution, retrospective study was conducted on 553 Chinese patients with OSCC who underwent R0 resection between January 2005 and October 2007. Survival curves were generated using the Kaplan-Meier method, and hazard function was used to analyse the annual recurrence hazard. RESULTS: The median recurrence-free survival time of these patients was 3.4 years. In univariate analysis, the favourable prognostic factors were gender, smoking status, a tumour length of ≤4.0 cm, tumour invasion thickness, normal level of squamous cell carcinoma (SCC) antigen, pathological T category and pathological N category. In multivariate analysis, pathological T category and pathological N category were independent prognostic factors. Overall, the recurrence hazard curve for the entire cohort showed that the first major recurrence surge began to increase from the first year at 22.97% and peaked at 1.3 years at 27.4% during follow-up. The second recurrence surge peaked during the seventh year at 13.0%. A lower recurrence risk was observed in patients with the following clinic-pathological characteristics: gender, smoking status and N0. CONCLUSIONS: We identify the presence of two peaks for recurrence risk in Chinese patients with resectable OSCC, which might contribute to choosing the optimal timing for adjuvant therapy after an operation to decrease or delay the recurrence hazard for patients with resectable OSCC.

Ectopic expression of B and T lymphocyte attenuator in gastric cancer: a potential independent prognostic factor in patients with gastric cancer.

It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co--inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer.

Time-varying pattern of postoperative recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC): results of a single-center study of 994 Chinese patients.

BACKGROUND: The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy. PATIENTS AND METHODS: This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function. RESULTS: The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups. CONCLUSIONS: The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy.

Comparison of endoscopic ultrasonography and multislice spiral computed tomography for the preoperative staging of gastric cancer - results of a single institution study of 610 Chinese patients.

BACKGROUND: This study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: A total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values). CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging.

Clinicopathologic significance of putative stem cell marker, CD44 and CD133, in human gastric carcinoma.

BACKGROUND AND OBJECTIVES: CD44 and CD133 have been reported as putative stem cell markers. However, the clinicopathologic significance of CD44 and CD133 expression in patients with gastric carcinoma (GC) has not been clearly elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the CD44 and CD133 expression in gastric carcinomas and normal mucosal tissues. Receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots, and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed CD44 and CD133 were observed in 27/152 (17.7%) and 64/152 (42.1%) of GCs and in 4/60 (6.7%) and 15/60 (25.0%) normal gastric mucosal tissues, respectively (P < 0.05, Fisher's exact test). High expression of CD44 was significantly correlated with tumor poorer differentiation, presence of distant metastasis, advanced TNM stage, and tumor relapse; and high expression of CD133 was positively associated with tumor invasion depth, presence of distant metastasis and advanced TNM stage. More importantly, high-expressed CD44 and CD133 were both associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our study introduces high expression of CD44 and CD133 as adverse independent prognostic factors in GC patients. The combined CD44 and CD133 expression may become a useful tool for identifying patients with different clinical outcomes.

Time-varying pattern of recurrence risk for gastric cancer patients.

This study analyzed the time-varying pattern of the recurrence risk for gastric cancer after surgery. A total of 1,222 gastric patients undergoing D2 resection surgery were studied retrospectively. The annual recurrence hazard curve for all of the populations showed one early peak and a late rise within 10 years after the surgery. The first major recurrence peak covers the first 3 years after the surgery, rising to a maximum at 1.5 years after surgery, followed by a decline until 7.5 years after the surgery, at which point the curve began to rise again. A subgroup analysis of this pattern also revealed that the curves of the patients with bigger tumors, poorly differentiated/undifferentiated adenocarcinomas, lymphatic/venous invasion, T3 and T4, node positive or with fewer lymph nodes retrieved were steeper. Chemotherapy can reduce the hazard rate for recurrence of gastric cancer. Our study confirms the time-varying pattern of the recurrence risk for gastric cancer, and it further supports the hypothesis of tumor dormancy after surgery. To effectively reduce the recurrence risk, new adjuvant therapies beyond chemotherapy may be needed.

CD33⁺/p-STAT1⁺ double-positive cell as a prognostic factor for stage IIIa gastric cancer.

Tumor-infiltrating immune cells are associated with tumor prognosis, although the type of immune cells responsible for local immune escape is still unknown. This study examined the relationship between gastric cancer survival and the density of immune cells, including CD8(+) T cells, CD20(+) B cells, and CD33(+)/p-STAT1(+) cells, which represent myeloid-derived suppressor cells, to evaluate the role of immune cells in the progression of gastric cancer. One hundred pathologically confirmed specimens were obtained from stage IIIa gastric cancers between 2003 and 2006 at Sun Yat-sen University Cancer Center, China. The density of tumor-infiltrating immune cells in tumor tissue was examined using immunohistochemical analysis. Clinicopathologic parameters and the survival rate were analyzed in relation to the density of immune cells. A high density of CD8(+) T cells and CD20(+) B cells was associated with a good clinical outcome, but a high density of CD33(+)/p-STAT1(+) cells was associated with a poor clinical outcome. Most importantly, the density of CD33(+)/p-STAT1(+) cells was an independent prognostic factor and inversely related to the infiltration of CD8(+) T cells. Although the infiltration of CD8(+) T cells and CD20(+) B cells is involved in the progression of gastric cancer, these data suggest that CD33(+)/p-STAT1(+) cells play a central role in the regulation of the local immune response, suggesting that CD33(+)/p-STAT1(+) cells might be therapeutic targets in gastric cancer.

The prognosis of gastric cancer patients with marginally elevated carcinoembryonic antigen (CEA) values after D2 radical gastrectomy.

AIM: To investigate the clinical significance of the postoperative serum carcinoembryonic antigen (CEA) levels in gastric cancer patients who underwent D2 radical gastrectomy and to identify the prognostic factors for patients with marginally elevated postoperative CEA levels. METHODS: We performed a retrospective study of 480 patients who were histologically diagnosed with gastric cancer and who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center between January 2004 and December 2009. The follow-up lasted until June 2011. Chi-squared tests and Kaplan-Meier methods were employed to compare the adverse events and prognoses. RESULTS: In this group of gastric cancer patients, the postoperative serum CEA level (P = 0.002) was an independent prognostic factor; the same was true for the histological T and N staging (P < 0.001 and P = 0.045, respectively). In the group of marginally elevated postoperative CEA level gastric cancer patients, univariate analysis demonstrated that tumor position (P = 0.042); histological grade (P = 0.002); and Boarrmann type (P = 0.003) were significant prognostic factors. Multivariate analysis showed that the tumor position (P = 0.003) and histological grade (P = 0.007) were independent prognostic factors for these patients. CONCLUSION: Our study showed that patients with normal postoperative CEA levels have a better prognosis. Furthermore, for marginally elevated postoperative CEA level gastric cancer patients, the tumor position and histological grade were two important factors for predicting the prognosis and the need for aggressive therapy.