Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor-κB pathway in ankylosing spondylitis.

OBJECTIVE: Our previous study reveals that proprotein convertase subtilisin/kexin type 9 (PCSK9) is positively related to inflammatory markers, T helper (Th)-17 cells, and treatment response in ankylosing spondylitis (AS) patients. Subsequently, this study aimed to explore the effect of PCSK9 on Th cell differentiation and its potential molecular mechanism in AS. METHODS: Serum PCSK9 was determined by enzyme-linked immunosorbent assay in 20 AS patients and 20 healthy controls (HCs). Then naïve CD4+ T cells were isolated from AS patients and infected with PCSK9 overexpression or knockdown adenovirus followed by polarization assay. Afterward, PMA (an NF-κB activator) was administrated. RESULTS: PCSK9 was increased in AS patients compared to HCs (p < .001), and it was positively related to Th1 cells (p = .050) and Th17 cells (p = .039) in AS patients. PCSK9 overexpression increased the CD4+ IFN-γ+ cells (p < .05), CD4+ IL-17A+ cells (p < .01), IFN-γ (p < .01), and IL-17A (p < .01), while it exhibited no effect on CD4+ IL-4+ cells or IL-4 (both p > .05); its knockdown displayed the opposite function on them. Moreover, PCSK9 overexpression upregulated the p-NF-κB p65/NF-κB p65 (p < .01), while it had no effect on p-ERK/ERK or p-JNK/JNK (both p > .05); its knockdown decreased p-NF-κB p65/NF-κB p65 (p < .01) and p-JNK/JNK (p < .05). Then, PMA upregulates p-NF-κB p65/NF-κB p65 (p < .001) and increased CD4+ IFN-γ+ cells, CD4+ IL-17A+ cells, IFN-γ, and IL-17A (all p < .01), also it alleviated the effect of PCSK9 knockdown on NF-κB inhibition and Th cell differentiation (all p < .01). CONCLUSION: PCSK9 enhances Th1 and Th17 cell differentiation in an NF-κB-dependent manner in AS, while further validation is necessary.

Serum PCSK9 is positively correlated with disease activity and Th17 cells, while its short-term decline during treatment reflects desirable outcomes in ankylosing spondylitis patients.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) participates in the autoimmune disease pathology by regulating T helper (Th) cell differentiation, NF-κB pathway, toll-like receptor 4, etc. This study intended to investigate the association of serum PCSK9 with disease activity, Th cells, and treatment response in ankylosing spondylitis (AS) patients. METHODS: Eighty-nine active AS patients were enrolled in this multicenter, prospective study. Serum was collected from AS patients at week (W)0, W4, W8, and W12, as well as from 20 osteoarthritis patients and 20 healthy controls after enrollment to detect PCSK9 by ELISA. Based on the ASAS40 response at W12, AS patients were classified as responders and non-responders. RESULTS: PCSK9 was increased in AS patients versus healthy controls (P < 0.001) and osteoarthritis patients (P = 0.006). In AS patients, PCSK9 was positively linked with C-reactive protein (CRP) (P = 0.003) and ASDAS-CRP (P = 0.017), but not with other clinical properties (P > 0.05). Besides, PCSK9 was negatively correlated with interleukin-4 (P = 0.034), positively associated with Th17 cells (P = 0.005) and interleukin-17A (P = 0.014), but did not relate to Th1 cells, interferon-γ, or Th2 cells (all P > 0.05). Additionally, PCSK9 was decreased from W0 to W12 in general AS patients (P < 0.001) and responders (P < 0.001) but remained unchanged in non-responders (P = 0.129). Moreover, PCSK9 was lower at W4 (P = 0.045), W8 (P = 0.008), and W12 (P = 0.004) in responders versus non-responders. Furthermore, the treatment options did not affect the PCSK9 level (P > 0.05). CONCLUSION: Serum PCSK9 is positively associated with disease activity and Th17 cells, while its short-term decline reflects desirable treatment response in AS patients.

Spatial-temporal distribution of pulmonary tuberculosis registered in Fuling District of Chongqing during the 13th Five-Year Plan period / 中国热带医学

@#Abstract: Objective To analyze the spatial-temporal characteristics of the active pulmonary tuberculosis (PTB) and the pathogenic positive PTB in Fuling District of Chongqing during the 13th Five-Year Plan period, so as to explore the clustering areas, and provide scientific basis for the precise prevention and control of tuberculosis in Fuling District. Methods The PTB registration data of 27 townships in Fuling District from 2016 to 2020 were collected. The descriptive analysis were used to describe the temporal and spatial distribution characteristics of patients, SaTScan9.0 and ArcGis10.6 was used for spatial-temporal scanning analysis and local auto-correlation analysis. The results were visualized by ArcGis10.6. Results A total of 4 038 case of active PTB patients were registered and a downward trend was observed in PTB during the 13th Five-Year Plan period in Fuling District. The average annual registration rate of PTB was 70.17/100 000, and the annual PTB registration rate declined by 8.21%. The peak of active PTB and etiological positive PTB were mainly concentrated in March and June respectively. The top five streets of cumulative active PTB patients registered were Lizhi street, Dunren street, Chongyi street, Ma 'an street and Jiangdong street, accounting for 60.18% of the total registered PTB patients during the 13th Five-Year Plan period. The top three average annual registration rates were Dunren street (101.35/100 000), Chongyi street (101.34/100 000) and Wulingshan Township (99.21/100 000). The registered PTB from 2016 to 2020 showed a global auto-correlation (Moran's I=0.64, P<0.0001). The "high-high" area of active PTB and the etiological positive PTB all covered Lizhi street, Jiangdong street and Longqiao street. By scanning analysis of spatial-temporal, the primary cluster of active PTB concentrated in the main urban area south of the Yangtze River in Fuling during January 2016 to December 2017, and the primary cluster of pathogenic positive PTB concentrated in the main urban area south of the Yangtze River in Fuling and Jiangdong street during January 2019 to December 2020. Conclusions During the 13th Five-Year Plan period, there was the spatial-temporal clustering of PTB in Fuling District, which mainly gathered in the main urban area south of the Yangtze River in Fuling district and surrounding streets centered on Lizhi street.

All optical metropolitan quantum key distribution network with post-quantum cryptography authentication.

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.

Sending or Not-Sending Twin-Field Quantum Key Distribution with Flawed and Leaky Sources.

Twin-field quantum key distribution (TF-QKD) has attracted considerable attention and developed rapidly due to its ability to surpass the fundamental rate-distance limit of QKD. However, the device imperfections may compromise its practical implementations. The goal of this paper is to make it robust against the state preparation flaws (SPFs) and side channels at the light source. We adopt the sending or not-sending (SNS) TF-QKD protocol to accommodate the SPFs and multiple optical modes in the emitted states. We analyze that the flaws of the phase modulation can be overcome by regarding the deviation of the phase as phase noise and eliminating it with the post-selection of phase. To overcome the side channels, we extend the generalized loss-tolerant (GLT) method to the four-intensity decoy-state SNS protocol. Remarkably, by decomposing of the two-mode single-photon states, the phase error rate can be estimated with only four parameters. The practical security of the SNS protocol with flawed and leaky source can be guaranteed. Our results might constitute a crucial step towards guaranteeing the practical implementation of the SNS protocol.

Association of laboratory parameters and genetic polymorphisms with ischemic stroke in Chinese Han population.

Numerous genetic polymorphisms and clinical laboratory parameters are associated with ischemic stroke (IS). However, the results of such studies have frequently been inconsistent. The aim of the present study was to evaluate associations between clinical laboratory parameters with genetic polymorphisms that influence the risk of IS in a Chinese Han population. Clinical laboratory parameters were measured by an automatic biochemical analyzer. Genotype and allele frequencies of the polymorphisms angiotensin-converting enzyme (ACE) D/I, methylene tetrahydrofolate reductase (MTHFR) C677T and ß-fibrinogen (ß-Fg) A/G, 455/148T/C were characterized by restriction fragment length polymorphism-PCR. Furthermore, the gene polymorphisms plasminogen activator inhibitor (PAI)-1-4G/5G and apolipoprotein E (ApoE) ε2,3,4 were characterized by allele-specific PCR. The associations of genotype and allele frequencies of the six risk genes in different groups with clinical laboratory parameters were analyzed by chi-square tests. The distribution maps of the polymorphisms of the six genes and clinical laboratory parameters were compared between a control group of 336 healthy individuals and 762 patients with IS. Certain laboratory parameters were associated with ACE I/D, ß-Fg-455 A/G and PAI-1 4G/5G. The D allele of ACE I/D was associated with high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C). Furthermore, high levels of fasting blood glucose, triglyceride and LDL-C were risk factors for IS. There were significant differences in the genotype frequencies of ACE I/D, ß-Fg-455 A/G and ß-Fg-148 T/C between the IS and the control group. In conclusion, clinical laboratory parameters were associated with the risk of polymorphisms of IS-related genes. The present results support the determination of a range of control values of clinical laboratory parameters for common genotypes in patients with diabetes and hyperlipidemia as a strategy for the early prevention of IS.

Curcumin protects the pancreas from acute pancreatitis via the mitogen­activated protein kinase signaling pathway.

Curcumin has been demonstrated to reduce markers of inflammation during acute pancreatitis (AP). However, the underlying mechanisms of the protective effects of curcumin are unknown. In the present study the effects of curcumin in an AP animal model and cell models was examined and the underlying mechanisms were investigated. An AP animal model was established by injection of 5% sodium taurocholate into the biliopancreatic duct of rats, and the cell model was established by treatment with 0.5 nM cerulein with an optimal concentration of lipopolysaccharide in AR42J rat pancreatic cancer cells. Amylase activity and arterial blood gas composition were assessed by automatic biochemical and blood gas analyzers. Pathological alteration of the pancreas was determined by hematoxylin and eosin staining. Interleukin (IL­6), tumor necrosis factor (TNF)­α and C­reactive protein (CRP) levels were measured by ELISA. Cell viability was determined by Cell Counting Kit­8 and protein expression levels were assessed by western blotting. Curcumin reduced the ascites volume after 12 and 24 h, the weight of pancreas after 12, 24 and 36 h of surgery, but also attenuated injury to the pancreas. Serum expression levels of TNF­α and CRP were reduced by curcumin. In addition, curcumin decreased the cell viability, amylase activity and the phosphorylation of p38 in AR42J cells, but did not affect the intracellular levels of IL­6 and TNF­α. Curcumin may lower the severity and inflammatory response via the mitogen­activated protein kinase­signaling pathway, to some extent. However, future studies are required to fully understand the protective effects of curcumin on AP.

The adsorption of NO, NH3, N2 on carbon surface: a density functional theory study.

To explore the adsorption mechanism of NO, NH3, N2 on a carbon surface, and the effect of basic and acidic functional groups, density functional theory was employed to investigate the interactions between these molecules and carbon surfaces. Molecular electrostatic potential, Mulliken population analyses, reduced density gradient, and Mayer bond order analyses were used to clarify the adsorption mechanism. The results indicate that van der Waals interactions are responsible for N2 physisorption, and N2 is the least likely to adsorb on a carbon surface. Modification of carbon materials to decorate basic or acidic functional groups could enhance the NH3 physisorption because of hydrogen bonding or electrostatic interactions, however, NO physisorption on a carbon surface is poor. Zig-zag sites are more reactive than armchair sites when these gas molecules absorb on the edge sites of carbon surface. Graphical abstract NH3, N2, NO adsortion on carbon surface.

MicroRNA-299-3p suppresses proliferation and invasion by targeting VEGFA in human colon carcinoma.

Accumulating evidences have shown that microRNAs (miRNAs) are vital regulators and possess huge capabilities in post-transcriptional control. Although a large number of miRNAs have been identified to be dysregulated in human cancers especially in colon cancer, our understandings of the function of most miRNAs are still largely limited. In this study, we have demonstrated that miR-299-3p plays a critical role in suppressing colon carcinoma progression by targeting Vascular Endothelial Growth Factor A (VEGFA). We observed that miR-299-3p was down-regulated in colon carcinoma tissues and colon cancer cell lines. The level of miR-299-3p was significantly negatively correlated with that of VEGFA mRNA level in colon carcinoma. More importantly, the low level of miR-299-3p predicted poor prognosis of colon cancer patients. Functionally, overexpression of miR-299-3p inhibited the proliferation and invasion of colon carcinoma cells and suppressed the growth of colon cancer xenografts in nude mice. Luciferase reporter assays showed that miR-299-3p could target VEGFA 3' UTR. In addition, up-regulation of miR-299-3p decreased VEGFA expression both in vitro and in vivo, showing that miR-299-3p plays a suppressive effect on VEGFA via post-transcriptional control. However, ectopical expression of VEGFA could abrogate this effect and also abolish miR-299-3p-induced inhibition of cell proliferation and invasion. Taken together, our study provides evidences showing that miR-299-3p functions as a suppressor in colon cancer by targeting VEGFA, suggesting that miR-299-3p might serve as a novel target for colon cancer therapy.

Norcantharidin Suppresses Colon Cancer Cell Epithelial-Mesenchymal Transition by Inhibiting the αvß6-ERK-Ets1 Signaling Pathway.

Norcantharidin (NCTD) is an efficacious anti-cancer drug that has been used in China for many years, but its underlying mechanism of action is still not fully understood. In the present study, we found that NCTD could induce morphological changes in colon cancer cells, causing a transition from a spindle-shaped morphology to a typical round or oval shape, which was indicative of a mesenchymal-epithelial transition (MET) process. Next, we investigated the mechanism by which NCTD induced the MET process. Using a transwell assay, we found that NCTD could suppress the migratory and invasive ability of colon cancer cells in a dose-dependent manner. Moreover, NCTD suppressed the expression of integrin αvß6, MMP-3, and MMP-9 as well as the polymerization of F-actin, further supporting its suppressive effect on migratory and invasive ability. Furthermore, the expression of αvß6, N-cadherin, vimentin and phosphorylated ERK was decreased, while the expression of E-cadherin was up-regulated. We verified that phosphorylated Ets1 was down-regulated substantially after treatment with NCTD. Taken together, our data demonstrated that NCTD could inhibit the EMT process of colon cancer cells by inhibiting the αvß6-ERK-Ets1 signaling pathway. This study revealed part of the mechanism through which NCTD could reverse the EMT process in colon cancer.

Integrin ß6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers and is expected to become the second leading cause of cancer death by 2030. Despite extensive efforts to improve surgical treatment, limited progress has been made. Increasing evidence indicates that integrin ß6 plays a crucial role in carcinoma invasion and metastasis. However, the expression and role of ß6 in PDAC remain largely unknown. In the present study, we investigated the expression of ß6 in PDAC and its potential value as a prognostic factor and therapeutic target. ß6 upregulation was identified as an independent unfavorable prognostic indicator. Integrin ß6 markedly promoted the proliferation and invasion of pancreatic carcinoma cells and induced ETS1 phosphorylation in an ERK-dependent manner, leading to the upregulation of matrix metalloprotease-9, which is essential for ß6-mediated invasiveness of pancreatic carcinoma cells. Accordingly, small interfering RNA-mediated silencing of integrin ß6 markedly suppressed xenograft tumor growth in vivo. Taken together, our results suggest that integrin ß6 plays important roles in the progression of pancreatic carcinoma and contributes to reduced survival times, and may serve as a novel therapeutic target for the treatment of PDAC.

Effect of vascular endothelial growth factor-C expression on lymph node metastasis in human cholangiocarcinoma.

The present study aimed to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in human cholangiocarcinoma tissues and its role in metastasis in vitro. A total of 65 biopsy samples of cholangiocarcinoma, plus the FRH-0201 cell line, were investigated. The expression of VEGF-C in the human cholangiocarcinoma specimens was evaluated by immunohistochemistry (IHC). The effect of VEGF-C on tumor cell migration and proliferation was measured by MTT and Transwell assays in the FRH-0201 cell line. According to the IHC results, the biopsies of human cholangiocarcinoma were stained positively for VEGF-C, with a positive rate of 75.4% (49/65). Moreover, VEGF-C was expressed at a higher level in the patients with lymph node metastasis than in those without lymph node metastasis. In vitro, VEGF-C exhibited marked growth stimulation below the concentration of 5 ng/ml and was able to promote cholangiocarcinoma cell migration significantly. These findings suggested that VEGF-C may be a useful factor to predict lymph node metastasis in cholangiocarcinoma tissues and indicates that VEGF-C plays a significant role in proliferation and migration in cholangiocarcinoma cells.

[Application of lymph node labeling with carbon nanoparticles in laparoscopic colorectal cancer surgery].

OBJECTIVE: To investigate the value of lymph node labeled with carbon nanoparticles in laparoscopic colorectal cancer resection. METHODS: The clinical data of 53 patients received laparoscopic radical colorectal surgeries in our department from March 2014 to July 2014 was retrospectively analyzed.Among these patients, carbon nanoparticles were injected into the periphery of the tumor under colonoscopy 1-3 days before the operation (the nanoparticle group) in 26 patients, while 27 patients received operation directly (the control group).The number of cleared lymph nodes, tiny lymph nodes (<5 mm), dyed lymph nodes, and lymph node metastatic rate were compared between the two groups. RESULTS: The two groups had no statistical difference in basic characteristics; 434 and 340 lymph nodes were dissected in the nanoparticle group and control group respectively.The average number of cleared lymph nodes(16.7 ± 3.2) in the nanoparticle group was significantly higher than that of the control group(12.6 ± 2.3) (P<0.001). Besides, both the average number and ratio of cleared tiny lymph nodes in the nanoparticle group were significant higher than those of the control group (P<0.001). Moreover, the rate of less than 12 detected lymph nodes in the nanoparticle group was markedly lower than that of the control group (0 vs 33.3%, P=0.001).There was no statistical difference in lymph node metastatic rate between the two groups (P=0.693). CONCLUSION: Application of lymph node labeled with carbon nanoparticles in laparoscopic colorectal cancer surgery could instruct lymph nodes dissection, improve lymph node detection rate, reduce tumor residual rate, improve the accuracy of pathological staging, and guide the postoperative adjuvant therapy.

Integrinß6-targeted immunoliposomes mediate tumor-specific drug delivery and enhance therapeutic efficacy in colon carcinoma.

PURPOSE: Adjuvant chemotherapy is one of the significant treatments for colon cancer in clinic. However, it does not achieve the desired therapeutic efficacy, largely due to chemotherapeutic resistance. Integrinß6 (ITGB6) is expressed in malignant colonic epithelia, but not in normal epithelia, and is associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, it is necessary to design therapeutic approaches for efficient and targeted drug delivery into ITGB6-positive cancer cells to improve chemotherapeutic efficacy in colon cancer. EXPERIMENTAL DESIGN: PEGylated liposomes were employed to design ITGB6-targeted immunoliposomes, which have ITGB6 monoclonal antibodies (mAbs) conjugated. We evaluated the ITGB6-targeted immunoliposomes internalization into colon cancer cells and examined 5-fluorouracil (5-FU)-induced cellular apoptosis produced by ITGB6-targeted immunoliposomes+5-FU. In addition, the biodistribution and antitumor efficiency of ITGB6-targeted immunoliposomes were observed in vivo. RESULTS: ITGB6-targeted immunoliposomes enhanced cellular internalization in ITGB6-positive colon cancer cells compared with liposomes. Furthermore, the ITGB6-targeted immunoliposome internalization was dependent on the ITGB6 expression level on cellular surface. ITGB6-targeted immunoliposomes decreased the 5-FU IC50 more than 90% in HT-29 and SW480ß6 cells relative to liposomes. Moreover, when loaded with 5-FU, ITGB6-targeted immunoliposomes produced an approximately 1.5-fold higher 5-FU-induced cellular apoptosis rate than liposomes. In vivo, the therapeutic activity of ITGB6-targeted immunoliposomes+5-FU was significantly superior, resulting in 25% to 35% reduction of tumor weight compared with 5-FU or liposomes+5-FU. CONCLUSIONS: ITGB6-targeted immunoliposomes provide a highly efficient approach for targeted drug delivery in colon cancer and thus offer the potential of a novel and promising anticancer strategy for clinical therapy.

Clinical significance of integrin ß6 as a tumor recurrence factor in follicular thyroid carcinoma.

BACKGROUND: Overexpression of integrin ß6 plays an important role in a variety of malignant tumor invasion and metastasis. METHODS: The expression levels of integrin ß6, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by immunohistochemistry with human follicular thyroid carcinomas. Then we investigated their correlation with clinical outcomes parameters, relationship, and the survival time. RESULTS: The integrin ß6 staining was expressed in cellular membrane and cytoplasm of follicular thyroid carcinoma cells. The MMP-2 and MMP-9 expressions were mainly found in cellular cytoplasm. In correlation with the clinical outcome parameters of 60 patients, there were significant statistical differences of integrin ß6, MMP-2, and MMP-9 expression levels in different size of tumor. Integrin ß6 and MMP-9 expressions have significant statistical differences in T classifications. MMP-2 and MMP-9 expressions have significant statistical differences in different M classification. Other clinical outcome parameters had no significant statistical differences. CONCLUSION: Integrin ß6 expression correlated significantly with MMP-9 expression, and may be a valuable recurrence indicator for follicular thyroid carcinomas.

High expression of matrix metalloproteinase-9 indicates poor prognosis in human hilar cholangiocarcinoma.

High expression of matrix metalloproteinase-9 (MMP-9) was found to be correlated with tumor progression and poor prognosis in a variety of carcinomas. However, few studies have investigated the role of MMP-9 in human hilar cholangiocarcinoma. In this study, a total of 58 patients with hilar cholangiocarcinoma who underwent curative resection were included in this study. The expression of MMP-9 was analyzed by immunohistochemistry using the streptavidin peroxidase complex method. The correlation of MMP-9 overexpression with clinicopathological features and survival time of patients was investigated. The results showed that MMP-9 overexpression was prominent in cancer cells and mainly localized in the cytoplasm. MMP-9 overexpression was observed in 46.5% tumors, which showed no correlation with clinicopathological parameters. Patients with high MMP-9 expression had a significantly poorer overall survival rate than those with negative or low MMP-9 expression (P = 0.038). Multivariate analysis confirmed that MMP-9 overexpression was an independent prognostic factor (P = 0.007). In conclusion, overexpression of MMP-9 is a valuable independent prognostic indicator in hilar cholangiocarcinoma.

Integrin αvß6 and transcriptional factor Ets-1 act as prognostic indicators in colorectal cancer.

BACKGROUND: Both transcriptional factor Ets-1 and integrin αvß6 play an important role in the development and progression of cancer. The aim of our study was to investigate the expression of Integrin αvß6 and Ets-1, two proteins' correlation and their clinical significance in colorectal cancerous tissues. RESULTS: The specimens were arranged into microarray using the immunohistochemistry method to investigate the expression of integrin αvß6 and transcriptional factor Ets-1 in these tissues. Among the 158 tissue specimens, 36.07% were positive for αvß6 expression, and 57.59% were positive for Ets-1 expression. There were obvious statistical differences existed regarding differentiation, N stage, M stage and TNM stage between αvß6 and Ets-1 positively and negatively expressing tumors. The correlation analysis confirmed the expression of αvß6 and Ets-1 were positively correlated in colorectal cancer. The Kaplan-Meier survival analysis showed that patients who were both αvß6 and Ets-1 positive relapsed earlier than those who were both αvß6 and Ets-1 negative; and the former group had much shorter survival time than the latter. And Cox model indicated that αvß6 and Ets-1 were the independent prognostic factors (RR = 2.175, P = 0.012 and RR = 3.903, P < 0.001). CONCLUSIONS: The expression of αvß6 and Ets-1 were positively correlated, and their expression degrees were associated with the differentiation, N stage, M stage and TNM stage of the tumors. Hence, the combination of αvß6 and Ets-1 can be used as a prognostic marker in colorectal cancer, especially for the early stage.

Interleukin-8 promotes cell migration through integrin αvß6 upregulation in colorectal cancer.

Colorectal cancer (CRC), which is notorious for high morbidity and mortality around the world, shows a predilection for metastasis to liver. Interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, has been reported to promote CRC cell migration and is associated with poor prognosis of CRC. However, the underlying molecular mechanism of IL-8-mediated migration remains obscure. In this study, we first demonstrated the cross talk between IL-8 and integrin αvß6. We analyzed 139 human CRC samples, and found that the immunohistochemical expression of αvß6 was significantly correlated with expression of IL-8. Furthermore, IL-8 increased the migration through integrin αvß6 in human CRC cells, and both CXCR1 and CXCR2 were primarily involved during the process. IL-8 upregulated αvß6 expression in a dose-dependent manner through activation of ERK and Ets-1 signaling pathway. Taken together, our results indicated that IL-8 enhances the migration of CRC cells by increasing αvß6 integrin expression through the ERK/Ets-1 pathway. Targeting integrin αvß6 in IL-8 expressing tumors might be a potential therapeutic strategy for CRC patients.