Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

The importance of intervertebral disc material model on the prediction of mechanical function of the cervical spine.

BACKGROUND: Linear elastic, hyperelastic, and multiphasic material constitutive models are frequently used for spinal intervertebral disc simulations. While the characteristics of each model are known, their effect on spine mechanical response requires a careful investigation. The use of advanced material models may not be applicable when material constants are not available, model convergence is unlikely, and computational time is a concern. On the other hand, poor estimations of tissue's mechanical response are likely if the spine model is oversimplified. In this study, discrepancies in load response introduced by material models will be investigated. METHODS: Three fiber-reinforced C2-C3 disc models were developed with linear elastic, hyperelastic, and biphasic behaviors. Three different loading modes were investigated: compression, flexion and extension in quasi-static and dynamic conditions. The deformed disc height, disc fluid pressure, range of motion, and stresses were compared. RESULTS: Results indicated that the intervertebral disc material model has a strong effect on load-sharing and disc height change when compression and flexion were applied. The predicted mechanical response of three models under extension had less discrepancy than its counterparts under flexion and compression. The fluid-solid interaction showed more relevance in dynamic than quasi-static loading conditions. The fiber-reinforced linear elastic and hyperelastic material models underestimated the load-sharing of the intervertebral disc annular collagen fibers. CONCLUSION: This study confirmed the central role of the disc fluid pressure in spinal load-sharing and highlighted loading conditions where linear elastic and hyperelastic models predicted energy distribution different than that of the biphasic model.

miR-874 inhibits gastric cancer cell proliferation by targeting SPAG9.

BACKGROUND: microRNAs (miRNAs) play essential roles in the development and progression of gastric cancer (GC). Although aberrant miR-874 expression has been reported in various human cancers, its role in GC remains obscure. METHODS: miR-874 expression was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) in 62 matched GC and adjacent normal tissues, as well as in GC cell lines and immortalized human gastric epithelial cells. CCK8 assay, colony formation assay, and flow cytometry were used to assess the role of miR-874 in GC cell proliferation and apoptosis in vitro. Additionally, to determine the effects of miR-874 on GC cell proliferation and apoptosis in vivo, BALB/c nude mice were injected with GC cells transfected with a miR-874 mimic. The role of miR-874 in SPAG9 expression was assessed by luciferase assay, Western blotting, and RT-qPCR. RESULTS: miR-874 was downregulated in GC cell lines and tissues. miR-874 overexpression in GC cells led to inhibition of cell proliferation and induction of apoptosis. Moreover, SPAG9 was identified as a direct miR-874 target, the expression of which was suppressed by miR-874. SPAG9 overexpression markedly promoted GC cell proliferation. CONCLUSIONS: miR-874 inhibited cell proliferation and induced apoptosis in GC cells. SPAG9 downregulation was crucial for the tumor-suppressive effects of miR-874. Hence, the miR-874/SPAG9 axis could serve as a novel therapeutic target in GC.

miR-7641 depletion suppresses proliferation of gastric cancer cells by targeting ARID1A.

Gastric cancer (GC) is lethal and there is an urgent need for improved understanding of this disease. Recent studies have reported that microRNAs (miRNAs) play increasingly important roles in the regulation of GC. In this study, we explored the target genes and effects of miR-7641 in GC. Our data showed that high miR-7641 expression was associated with low expression of ARID1A in GC tissue. miR-7641 expression promoted GC cell proliferation and colony formation. Luciferase reporter assay results confirmed that ARID1A was a target gene of miR-7641. Furthermore, downregulation of ARID1A expression caused a significant increase in GC cell proliferation. In vivo depletion of miR-7641 reduced tumor volume and weight and increased ARID1A and Ki67 expression as well as a decreased terminal-deoxynucleotidyl transferase-mediated nick end labeling in mouse tumor tissues. Conversely, ARID1A silencing reversed the suppressive effects of miR-7641 inhibitors on GC cells. Overall, these findings indicate that miR-7641 is a promising novel prognostic biomarker of GC and may represent a novel target for clinical management of GC.

[Effect of allergic rhinitis on disease condition and treatment in patients with juvenile-onset systemic lupus erythematosus].

OBJECTIVE: To investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE). METHODS: The clinical data of 96 children diagnosed with JSLE were collected, and according to the presence or absence of AR or other allergic diseases, they were divided into AR group (n=44), non-AR group (n=20), and non-allergic group (n=32). The children in the AR group were randomly administered with or without intervention (n=22 each). All the children were given standard JSLE treatment. The systemic lupus erythematosus disease active index (SLEDAI) and application of hormones and immunosuppressants were compared between groups. RESULTS: The AR and non-AR groups had significantly higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants used than the non-allergic group before treatment (P<0.05), while there were no significant differences between the AR and non-AR groups (P>0.05). After one month of treatment, the AR group with intervention had significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids than the AR group without intervention (P<0.05), while there was no significant difference in the application of immunosuppressants between these two groups (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants than the AR group without intervention (P<0.05). CONCLUSIONS: JSLE combined with allergic diseases such as AR has an adverse effect on disease condition and treatment, and the intervention for AR helps with the control of JSLE.

Fibroblast growth factor receptor 4 as a potential prognostic and therapeutic marker in colorectal cancer.

The purpose of the study was to explore the significance of FGFR4 protein expression in colorectal cancer. Immunohistochemistry showed 46.8% (148/316) tumors positive for FGFR4 and 7.3% (23/316) for adjacent normal specimens. FGFR4 positivity was correlated with shortened disease free survival (DFS) and overall survival (OS). Multivariate analysis revealed that FGFR4 was an independent prognostic factor. FGFR4 silencing markedly reduced the migration and invasion capacity of colorectal cancer cell lines. These results suggest FGFR4 is a potential prognostic and therapeutic marker for colorectal cancer.

Over-expression of VEGF and MMP-9 in residual tumor cells of hepatocellular carcinoma after embolization with lipidol.

The expression and implication of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in residual hepatic tumor cells after lipiodol embolization were investigated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group (n=20) and lipiodol group (n=20). For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using enzyme-linked immunosorbent assay (ELISA). A three-step immunohistochemical technique (ABC) was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group (1.42±0.29 ng/mL) than in the control group (1.12±0.21 ng/mL) (P<0.01). Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group (62.13%±7.69%) than in the control group (53.16%±9.17%) (P<0.05). Similarly, the MMP-9 expression in the residual tumor cells was higher in the lipiodol group. The mRNA levels of VEGF (2.9313±2.4231) and MMP-9 (3.5721±1.6107) in the lipiodol group were significantly higher than those in the control group (1.5728±0.9453 and 1.7573±1.0641, respectively, P<0.05). Therefore, it was reasonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.

Long intergenic noncoding RNA 00665 promotes proliferation and inhibits apoptosis in colorectal cancer by regulating miR-126-5p.

Long intergenic noncoding RNAs (lincRNAs) regulate a series of biological processes, and their anomalous expression plays critical roles in the progression of multiple malignancies, including colorectal cancer (CRC). Although many studies have reported the oncogenic function of LINC00665 in multiple cancers, few studies have explored its role in CRC. The aim of this study was to assess the effect of LINC00665 on the malignant behaviors of CRC and explore the underlying regulatory mechanism of LINC00665. LINC00665 was significantly upregulated in CRC. A loss-of-function assay revealed that LINC00665 downregulation inhibited the proliferation and promoted the apoptosis of CRC cells, which was mediated by cyclin D1, CDK4, caspase-9 and caspase-3. Through mechanistic exploration, we found that miR-126-5p directly bound to LINC00665. Moreover, LINC00665 and miR-126-5p both regulated PAK2 and FZD3 expression. Mechanistically, miR-126-5p was predicted and further verified as a target of both PAK2 and FZD3. These findings demonstrate that LINC00665 might play an important pro-proliferative and antiapoptotic role in CRC and might be a potential biomarker and a new therapeutic target for CRC.

Isolated synchronous Virchow lymph node metastasis of sigmoid cancer: A case report.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. Lymphatic metastases of this tumor are mostly confined to the regional lymph nodes, and distant supraclavicular lymph node metastases are very rare. CASE SUMMARY: In this report, we describe a patient with sigmoid carcinoma and isolated synchronous supraclavicular lymph node metastases. A 56-year-old male presented with a left cervical mass that was confirmed as a lymph node metastasis from sigmoid cancer by several auxiliary examinations. After 6 cycles of chemotherapy with the 5-fluorouracil, leucovorin and oxaliplatin + cetuximab regimen, the sigmoid colon tumor and Virchow's lymph node metastasis were significantly smaller than before treatment, and no new metastatic sites were observed. Considering the effects of chemotherapy on quality of life, resection of the primary tumor was performed followed by 4 cycles of chemotherapy with the original chemotherapy regimen. Virchow's lymph node dissection was selected by mutual consultation between the patient and us. After the second surgery, the patient received capecitabine and cetuximab chemotherapy and did not experience recurrence or metastasis during follow-up. CONCLUSION: In conclusion, supraclavicular lymph node metastasis without any other solid organ metastasis is a potential metastatic pathway for CRC. In addition, after resection of the primary lesion, postoperative chemotherapy combined with supraclavicular lymph node dissection is feasible for the treatment of patients with CRC and isolated synchronous Virchow's lymph node metastases.

Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis.

BACKGROUND: Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines. AIM: To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs). METHODS: Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared. RESULTS: Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group (P = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, P = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups. CONCLUSION: Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.

Use of the alkaline phosphatase to prealbumin ratio as an independent predictive factor for the prognosis of gastric cancer.

BACKGROUND: Gastric cancer (GC) is characterized by a low 5-year survival rate. The prognosis is still not satisfactory although it has significantly improved due to developments in medicine. Thus, the identification of more efficient indices for the evaluation of GC prognosis is required. We propose, for the first time, that the alkaline phosphatase (ALP) to prealbumin (PA) ratio (APR) can be used as an independent prognostic factor in GC. AIM: To evaluate the prognostic value the APR in GC. METHODS: According to the exclusion strategy, we collected the preoperative serologic examination results and clinical information of 409 GC patients treated in Shandong Provincial Hospital from January to December, 2016. By calculating the APR, the neutrophil and lymphocyte ratio (NLR), C-reactive protein (CRP) and albumin (ALB) ratio, platelet and lymphocyte ratio, lymphocyte and monocyte ratio, and the relationship with clinical information, we verified the role of preoperative APR ratio in the prognosis of GC. In addition, we used a Cox model combined with the APR and tumor stage to demonstrate its efficacy in assessing the prognosis of GC patients. RESULTS: Preoperative APR was an independent prognostic factor for GC. The median age of patients in the APR-high group was greater compared with that in the APR-low group. Patients with a higher APR had a more advanced clinical stage, higher neutrophil to lymphocyte, CRP to ALB, and platelet to lymphocyte ratios, but a lower lymphocyte to monocyte ratio (P < 0.05). The APR-high group also had higher glycoprotein antigen 199 and carbohydrate antigen 125 levels than the APR-low group (P < 0.05). Median overall survival and disease-free survival were significantly longer in the APR-low group than in the APR-high group. In addition, a Cox model based on the APR and tumor stage was more effective in evaluating the prognosis of patients than models based on stage alone or stage plus the NLR. CONCLUSION: A higher APR is an independent and negative prognostic factor for GC. The prognosis of GC can be better evaluated using a Cox model based on the APR and stage.

Identification of New Therapeutic Targets for Gastric Cancer With Bioinformatics.

We aimed to identify new targets affecting gastric cancer (GC) prognosis. Six target genes were identified from hub genes based on their relationship with important factors affecting tumor progression, like immune infiltration, purity, tumor mutation burden (TMB), and tumor microenvironment (TME) score. The effect of target genes' somatic mutations and copy number alteration (CNA) was examined to determine their effect on GC prognosis. Six target genes (FBN1, FN1, HGF, MMP9, THBS1, and VCAN) were identified. Reduced expression of each target gene, except MMP9, indicated better prognosis and lower grade in GC. FBN1, THBS1, and VCAN showed lower expression in stage I GC. Non-silencing mutations of the six genes played a role in significantly higher TMB and TME scores. THBS1 mutation was associated with earlier stage GC, and VCAN mutation was associated with lower grade GC. However, patients with target gene CNA displayed higher tumor purity. MMP9, THBS1, and VCAN CNA was associated with lower grade GC, while FBN1 CNA reflected earlier T stage. Additionally, the target genes may affect GC prognosis by influencing multiple oncogenic signaling pathways. FBN1, FN1, HGF, MMP9, THBS1, and VCAN may be new GC prognostic targets by affecting tumor purity, TMB, TME score, and multiple oncogenic signaling pathways.

Chemokine receptor 4 expression is correlated with the occurrence and prognosis of gastric cancer.

Gastric cancer (GC) is a common tumor with a low 5-year survival rate. The chemokine receptor 4 (CXCR4) protein contributes to the progression and prognosis of GC, but the relationship between CXCR4 and immune infiltration, somatic copy number alteration (SCNA), tumor purity, tumor mutation burden (TMB), cytolytic activity (CYT), and drug sensitivity in GC is poorly understood. This study aimed to systematically explore the role of CXCR4 in GC. Microarray and RNA-seq data were collected from the Gene Expression Omnibus and The Cancer Genome Atlas. Our analysis shows that CXCR4 is correlated with various types of immune cells. Patients with high CXCR4 expression had a higher fraction of B cells and CD8+ T cells, and a lower fraction of CD4+ T cells. In addition, high CXCR4 expression was associated with more advanced tumor stage, worse prognosis and higher stromal score, immune score, and cytolytic activity (P < 0.05). High CXCR4 expression also correlated with lower tumor purity and TMB. In summary, our analyses suggest that CXCR4 may affect the progression and prognosis of GC by influencing immune infiltration, TMB, CYT, tumor purity, and drug sensitivity.

Function of fibroblast growth factor 2 in gastric cancer occurrence and prognosis.

The present study aimed to explore the role of fibroblast growth factor 2 (FGF2) in the development and prognosis of gastric cancer (GC). The relationship between FGF2 mRNA expression levels and the clinical characteristics of GC was investigated using microarray data from four GC cohorts involving 726 patients obtained from the Gene Expression Omnibus. The results of the present study indicated that FGF2 expression levels were an independent factor affecting the prognosis of GC. The primary functions of FGF2 were related to cell adhesion and angiogenesis, and patients with high levels of FGF2 expression had poorer TNM staging and prognosis; these differences were statistically significant. In terms of immune infiltration, a higher extent of M2 macrophage intrusion was observed in patients with higher levels of FGF2. However, the degree of infiltration by dendritic and CD4+ T cells was lower, and this difference was statistically significant. Multivariate Cox proportional hazards model analysis revealed that age, TNM staging and FGF2 expression levels were independent prognostic factors for GC. In summary, FGF2 expression was demonstrated to be an independent prognostic factor in GC, and higher levels of FGF2 may promote the progression of this malignancy.

International consensus on natural orifice specimen extraction surgery (NOSES) for gastric cancer (2019).

At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.

Usefulness of large-section cytokeratin 20 in the detection of intestinal wall infiltration and mesangial metastasis in patients with middle and lower rectal cancer.

OBJECTIVE: The objective of the study was to evaluate the usefulness of large-section cytokeratin 20 (CK20) staining technique in the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer. MATERIALS AND METHODS: A total of 62 patients with rectal cancer in the middle and lower segment were studied on large slices stained with CK20. Logistic regression was used to analyze the clinicopathologic factors related to distal low and middle rectal cancer metastasis to the mesorectum and rectal wall. RESULTS: Two types of distal metastasis of the tumor were observed in the rectal wall in 18% (11/62) of the patients: submucosal invasion and muscularis propria invasion. The extent of distal metastasis to the rectal wall was around 0.5-1.0 cm. Four types of distal metastasis occurred in the mesorectum: lymph node invasion, blood and lymphatic vessel invasion, perineural invasion, and isolated neoplastic microfoci. Distal metastasis to the mesorectum was observed in 24% (15/62) of the patients. The extent of metastasis to the mesorectum was around 0.5-4.0 cm. Another three patients with microcapillary invasion in the distal mesorectum were observed by immunohistochemistry, as it was difficult to determine the spread by conventional hematoxylin and eosin staining. CONCLUSION: The large-section CK20 staining technique is useful for the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer.

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.

Promotion of Sema4D expression by tumor-associated macrophages: Significance in gastric carcinoma.

AIM: To study the role of semaphorin 4D (Sema4D) expression promoted by tumor-associated macrophages (TAMs) in gastric carcinoma cells and its clinical significance in the invasion and metastasis of gastric carcinoma. METHODS: CD68 and Sema4D expression was analyzed in gastric carcinoma and adjacent normal tissues from 290 patients using the immunohistochemical streptavidin-peroxidase method, and their relationships with clinicopathological features were evaluated. Human M2 macrophages were induced in vitro and co-cultured in non-contact with gastric carcinoma SGC-7901 cells. Changes in the secretory Sema4D level in the SGC-7901 cell supernatant were measured using an enzyme-linked immunosorbent assay. The effects of TAMs on SGC-7901 cell invasion and migration were assessed with invasion and migration assays, respectively. RESULTS: CD68 and Sema4D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues (71.7% vs 33.8% and 74.5% vs 42.8%, respectively; P < 0.01). CD68 and Sema4D protein expression was significantly associated with histological differentiation, TNM stage, and lymph node metastasis (P < 0.05), and their expression levels were positively correlated with one another (r = 0.467, P < 0.01). In the in vitro experiment, secretory Sema4D protein expression was significantly increased in the supernatant of SGC-7901 cells co-cultured with TAMs compared with the blank control (1224.13 ± 29.43 vs 637.15 ± 33.84, P < 0.01). Cell invasion and metastasis were enhanced in the Transwell invasion and migration assays (P < 0.01). CONCLUSION: TAMs promote the invasion and metastasis of gastric carcinoma cells possibly through upregulated secretory Sema4D protein expression. Combined detection of TAM markers, CD68 and Sema4D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.

Mismatch repair-deficient status associates with favorable prognosis of Eastern Chinese population with sporadic colorectal cancer.

The present study aimed to investigate the expression level of DNA mismatch repair gene (MMR) in in sporadic colorectal cancer (SCRC) in eastern China, and to investigate the association between MMR status and prognosis of patients with SCRC. Patient archives from the Department of Gastrointestinal Surgery of Weihai Municipal Hospital (Weihai, China) were retrospectively collected between January 2011 and January 2012. Of the 221 consecutive patients identified, 192 patients who met the criterion were deemed eligible for inclusion. Immunohistochemistry (IHC) was conducted to detect the expression of MMR proteins MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2, mismatch repair system component (PMS2) expression and mutation in sporadic colorectal cancer (SCRC). Kaplan-Meier plots and log-rank tests were performed to conduct survival analysis and Cox proportional hazard regression models were conducted to determine independent prognostic factors. The total rate of deficient MMR (dMMR) was 14.58% (28/192): MSH6, 0.52% (1/192); PMS2, 4.17% (8/192); MSH2/MSH6, 3.65% (7/192); and MLH1/PMS2, 6.25% (12/192). The dMMR group had a significantly longer overall survival time compared with proficient MMR (pMMR) group (P=0.017). Disease-free survival time of dMMR group was also longer than pMMR group (P=0.027). Multivariate analysis using the Cox regression model confirmed that MMR status was an independent prognostic factor for SCRC. Loss of MMR expression was indicative of a favorable outcome for patients with SCRC, and MMR status could be viewed as an independent prognostic factor.