Loss of ARID1A Expression is Associated with Systemic Inflammation Markers and has Important Prognostic Significance in Gastric Cancer.

Abstract Background: The tumor suppressor gene AT-rich interactive domain 1A (ARID1A) and systemic inflammatory response (SIR) have been reported to be related to the sensitivity of immunotherapy. This study intended to explore the relationship between ARID1A expression and SIR, and to further elucidate the prognostic value of ARID1A expression in gastric cancer (GC).Methods: The mRNA and protein expression of ARID1A were detected in 272 formalin-fixed paraffin-embedded (FFPE) tumor tissues. The data of nine systemic inflammation markers were collected one week before gastrectomy. Univariate and multivariate COX analysis were used to screen out independent predictors of GC.Results: Negative expression of ARID1A protein was related to GC with microsatellite instability-high (MSI-H) (p=0.033), positive programmed cell death-ligand 1 (PD-L1) (p=0.005) and lower albumin level (p=0.0064). Low expression of ARID1A mRNA was common in GC with abnormal E-cadherin (p=0.020) and higher platelet/lymphocyte ratio (PLR) (p=0.0391). Multivariate COX analysis showed that the expression of ARID1A protein (p=0.023), age (p=0.004), T stage (p=0.009) and N stage (p=0.009) were independent predictors of GC. The nomogram established by independent predictors can accurately evaluate the survival risk of patients with GC.Conclusions: The loss of ARID1A protein expression was associated with MSI-H subtype and high expression of PD-L1 in GC. Negative ARID1A protein and low expression of mRNA were associated with aberrant systemic inflammatory markers. Expression of ARID1A protein had important prognostic significance in GC.

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Prognostic Impact of Postoperative Systemic Inflammatory Response in Patients with Stage II/III Gastric Cancer

10.21203/rs.3.rs-667633/v1 ◽

2021 ◽

Author(s):

Kenji Kuroda ◽

Takahiro Toyokawa ◽

Yuichiro Miki ◽

Mami Yoshii ◽

Tatsuro Tamura ◽

...

Keyword(s):

Gastric Cancer ◽

Inflammatory Response ◽

Systemic Inflammation ◽

Early Phase ◽

Prognostic Significance ◽

Infectious Complications ◽

Systemic Inflammatory Response ◽

Stage Ii ◽

Prognostic Impact ◽

Maximum Serum

Abstract Background: Several studies have shown that postoperative infectious complications correlate with poor prognosis in various malignancies, but the prognostic significance of the postoperative inflammatory response in patients with gastric cancer remains unclear. This study examined whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with stage II/III gastric cancer.Methods: This study retrospectively reviewed 444 consecutive patients who underwent radical gastrectomy for stage II/III gastric cancer. We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers.Results: In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p<0.001, p<0.001 and p=0.011, respectively) and relapse-free survival (RFS) (p<0.001, p=0.001 and p<0.001, respectively). Multivariate analysis revealed that high-CRPmax (>9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.18–2.42, p=0.004) and RFS (HR 1.42, 95%CI 1.02–1.98, p=0.038), while WBCmax and infectious complications were not. Conclusion: CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.

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Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer

Tumor Biology ◽

10.1177/1010428317694547 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769454 ◽

Cited By ~ 3

Author(s):

Takahiko Kobayashi ◽

Junich Ishida ◽

Yuichi Shimizu ◽

Hiroshi Kawakami ◽

Goki Suda ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Growth ◽

Tumor Suppressor ◽

Protein Expression ◽

Cancer Cells ◽

Rna Binding ◽

Suppressor Gene ◽

Binding Motif ◽

Gastric Cancer Cells ◽

Rna Binding Motif 5

RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor–node–metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5–silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.

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DCC and TS protein expression in resected gastric cancer: A Hellenic Cooperative Oncology Group Study

Open Medicine ◽

10.2478/s11536-007-0054-y ◽

2008 ◽

Vol 3 (1) ◽

pp. 29-39

Author(s):

Aristotle Bamias ◽

George Fountzilas ◽

Michael Michael ◽

Christos Konstantaras ◽

Eleftheria Vrettou ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Protein Expression ◽

Prognostic Significance ◽

Staining Intensity ◽

Lymph Node Involvement ◽

Independent Prognostic Factor ◽

Node Involvement ◽

Dcc Gene ◽

Cause Specific Survival

AbstractThere is a high risk of relapse after resection of gastric cancer. We studied the prognostic significance of the deleted colorectal cancer (DCC) gene and thymidylate synthase (TS) protein expression after resection of gastric cancer. Protein expression in the primary tumor of 146 patients with serosal and/or lymph node involvement was studied immunohistochemically by using anti-DCC and anti-TS monoclonal antibodies. DCC expression was found in 69.9%, while low TS staining intensity (0+,1+) and focal staining (<25% of tumor cells stained) were found in 44.6% and 33.8%, respectively. Overall survival (OS) was significantly longer in patients with DCC (p=0.014) negative tumors. TS expression was not an independent prognostic factor. Lack of DCC expression was associated with significantly longer cause-specific survival (CSS) (p=0.040) after curative resection. In conclusion, DCC expression is an independent prognostic factor in patients undergoing resection of gastric cancer while TS expression was not associated with the prognosis in our study.

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Prognostic Significance of p53 Protein Expression in Early Gastric Cancer

Pathology & Oncology Research ◽

10.1007/s12253-010-9333-z ◽

2010 ◽

Vol 17 (2) ◽

pp. 349-355 ◽

Cited By ~ 18

Author(s):

Andrea Rodrigues Gonçalves ◽

Antonio Jose Vasconcellos Carneiro ◽

Ivanir Martins ◽

Paulo Antonio Silvestre de Faria ◽

Maria Aparecida Ferreira ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Protein Expression ◽

P53 Protein ◽

Prognostic Significance ◽

P53 Protein Expression

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Protein expression of tumor suppressor gene p16 in gastric cancer

Digestive and Liver Disease ◽

10.1016/s1590-8658(01)80468-0 ◽

2001 ◽

Vol 33 ◽

pp. A79

Author(s):

A. Rocco ◽

L. Schandl ◽

Z. Tulassay ◽

P. Malfertheiner ◽

M. Ebert ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Suppressor ◽

Protein Expression ◽

Tumor Suppressor Gene ◽

Suppressor Gene

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ASSESSMENT OF SYSTEMIC INFLAMMATION MARKERS IN HIV INFECTED OPIATE USERS

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2018-10-2-90-95 ◽

2018 ◽

Vol 10 (2) ◽

pp. 90-95

Author(s):

A. N. Kholodnaya ◽

D. A. Lioznov ◽

S. L. Nikolaenko ◽

E. A. Blokhina ◽

T. S. Yaroslavtseva ◽

...

Keyword(s):

Inflammatory Response ◽

Systemic Inflammation ◽

Interleukin 6 ◽

Prognostic Significance ◽

Hiv Positive ◽

Inflammation Markers ◽

Opioid Use ◽

Opiate Use ◽

History Of ◽

D Dimer

Interleukin 6 and D-dimer known as chronic systemic inﬂammation markers shown prognostic significance in course of HIVdisease. Association between opioid use and systemic inﬂammation response are still elucidate. Objective: аssess plasma levels of IL-6 and D-dimer in HIV-positive patients in groups formed on the base of opiate use activity. Materials and methods. Crosssectional study of 346 HIV-positive ART-naive individuals. Participants were categorized into 3 groups according to their history of opioid use: 1) current opioid use — past 30 day opioid use; 2) «ever» opioid use — no use in past 30 days; 3) «never» opioid use. Results. Рarticipants with current opioid use had higher log-transformed IL-6 (0,4 [ s 1,0]; p<0,0001) and D-dimer (-0,6 [ s 0,9]; p<0,0001) levels than participants who reported «ever» (-0,1 [ s 1,0] and -0,9 [ s 0,8]), or «never» (-0,4 [ s 0,7] and 1,3 [ s 0,7]) opioid use. Conclusion. Оpioid use in HIV-positive participants is associated with higher inﬂammatory response.

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Results of the non-interventional observational program: Influence of Novel COroNavirus on the condition of patients with liver and gastrointestinal Tract diseases and the effect of Ursodeoxycholic acid drugs and Rebamipide on the course of COVID-19 infection (CONTUR)

Medical Council ◽

10.21518/2079-701x-2021-21-1-106-119 ◽

2022 ◽

pp. 106-119

Author(s):

I. N. Tikhonov ◽

V. T. Ivashkin ◽

M. S. Zharkova ◽

M. V. Maevskaya ◽

S. N. Koloteeva ◽

...

Keyword(s):

Abdominal Pain ◽

Gastrointestinal Tract ◽

Liver Injury ◽

Systemic Inflammation ◽

Gastrointestinal Diseases ◽

Albumin Level ◽

Russian Society ◽

Inflammation Markers ◽

Obesity And Diabetes ◽

Observational Program

Intriduction. The course and outcome of COVID-19 infection in patients with liver and gastrointestinal tract diseases remain poorly understood. The article presents a multicenter non-interventional observational program conducted by the Russian Society for the Study of the Liver.Aim. To study the relationship between COVID-19 and injuries of gastrointestinal tract and liver, to assess the effect of therapy with UDCA and Rebamipide on the course and outcome of COVID-19 infection. Materials and methods. 460 patients were enrolled in the study, of which 46% were patients with gastrointestinal and liver diseases. Some patients received Rebamipide and UDCA at a dose of 15 mg/kg body weight, followed by assessment of the clinical and laboratory parameters.Results. In the study group, more severe lung injury and the course of infection were observed. The investigators detected three phenotypes of gastrointestinal tract injury: dyspeptic, diarrheal and painful. The latter was more common in patients with gastrointestinal diseases. Liver injury occurred in 87% of patients with COVID-19 (of which 44% had a history of liver disease). Increased ALT and AST were more often recorded in patients with obesity and diabetes mellitus and correlated with the severity of the infection. An inverse relationship was found between the albumin level and death and transfer to mechanical ventilation. At least 5-day Rebamipide therapy leads to reduction of diarrhea and abdominal pain (p < 0.00001 and p = 0.002), decrease in the levels of systemic inflammatory markers (CRP and ferritin, p<0.00001). The use of UDCA leads to a decrease of the systemic inflammation markers: ferritin and is associated with a significant decrease/normalization of ALT levels (p < 0.00001).Conclusions. In patients with diseases of the gastrointestinal tract and liver, COVID-19 develops in a more severe form and symptoms of gastrointestinal tract injury may prevail in the clinical picture. The severity of liver injury correlates with the severity of COVID-19 and a poor prognosis. Rebamipide reduces diarrhea and abdominal pain. UDCA prevents or reduces liver injury in COVID-19 infection. Both drugs reduce the level of systemic inflammation markers.

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ARID1A deficiency in EBV-positive gastric cancer is partially regulated by EBV-encoded miRNAs, but not by DNA promotor hypermethylation

Carcinogenesis ◽

10.1093/carcin/bgaa123 ◽

2020 ◽

Author(s):

Koji Kase ◽

Motonobu Saito ◽

Shotaro Nakajima ◽

Daisuke Takayanagi ◽

Katsuharu Saito ◽

...

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Methylation Status ◽

Computational Prediction ◽

Suppressor Gene ◽

Epigenetic Modifications ◽

The Cancer Genome Atlas ◽

Transcriptional Gene Silencing ◽

Mrna Levels

Abstract AT-rich interactive domain 1A (ARID1A), which is a tumor suppressor gene, is frequently mutated in Epstein-Barr virus-positive gastric cancer [EBV (+) GC]. While most ARID1A mutations in GC are truncating mutations, leading to loss of ARID1A protein expression, epigenetic modifications appear to contribute to ARID1A deficiency in EBV (+) GC harboring wild-type ARID1A. Based on the significant role of epigenetic modifications in EBV (+) GC that contributes to ARID1A deficiency, the methylation status of ARID1A was evaluated in EBV-infected cells and GC patients using a publicly available microarray and the Cancer Genome Atlas (TCGA) database. EBV-encoded miRNAs that potentially target ARID1A were identified as an additional epigenetic modulator by computational prediction. In vitro experiments were conducted to evaluate how EBV-encoded miRNAs affected ARID1A mRNA and protein levels. In clinical GC samples, the expression of predicted miRNAs and ARID1A and the mutation status of ARID1A was evaluated. As results, ARID1A was not hypermethylated in EBV (+) GC samples or EBV-infected GC cells. EBV infection did not alter ARID1A mRNA levels, suggesting that ARID1A protein deficiency was caused by post-transcriptional gene silencing in ARID1A-WT EBV (+) GC. Overexpression of miR-BART11-3p and miR-BART12, which were identified as miRNAs that potentially bind ARID1A, suppressed ARID1A protein expression in MKN7 and NCI-N87 cells. Highly expressed miR-BART11-3p and miR-BART12 were correlated with decreased ARID1A levels in GC tumors which did not harbor ARID1A mutations. The present findings revealed that ARID1A expression was epigenetically regulated by miR-BART11-3p and miR-BART12 in EBV (+) GC.

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