TRF-Val-CAC-016 Modulates the Transduction of CACNA1d-Mediated MAPK Signaling Pathways to Suppress the Proliferation of Gastric Carcinoma

Background: As a new kind of non-coding RNAs (ncRNAs), tRNA derivatives play an important role in gastric carcinoma (GC). Nevertheless, the underlying mechanism tRNA derivatives were involved in was rarely illustrated. Methods: We screened out the tRNA derivative, tRF-Val-CAC-016, based on the tsRNA sequencing and demonstrated the effect tRF-Val-CAC-016 exerted on GC proliferation in vitro and in vivo. We applied Dual-luciferase reporter assay, RIP assay, and bioinformatic analysis to discover the downstream target of tRF-Val-CAC-016. Then CACNA1d was selected, and the oncogenic characteristics were verified. Subsequently, we detected the possible regulation of the canonical MAPK signaling pathway to further explore the downstream mechanism of tRF-Val-CAC-016. Results: As a result, we found that tRF-Val-CAC-016 was low-expressed in GC, and upregulation of tRF-Val-CAC-016 could significantly suppress the proliferation of GC cell lines. Meanwhile, tRF-Val-CAC-016 regulated the canonical MAPK signaling pathway by targeting CACNA1d. Conclusions: tRF-Val-CAC-016 modulates the transduction of CACNA1d-mediated MAPK signaling pathways to suppress the proliferation of gastric carcinoma. This study discussed the function and mechanism of tRF-Val-CAC-016 in GC for the first time. The pioneering work has contributed to our present understanding of tRNA derivative, which might provide an alternative mean for the targeted therapy of GC.

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Gastric carcinoma is the fourth most prevalent cause of cancer-related deaths worldwide because of dismal prognosis and few therapeutic options. Accumulated studies have indicated that targeting lysyl oxidase (LOX) family members may serve as an anticancer strategy. Nevertheless, the specific mechanisms of LOX in stomach carcinoma are still unclear. In this study, we demonstrated that LOX is significantly different in 13 types of cancers and may act as a potential therapeutic target, especially in stomach carcinoma. Moreover, overexpression of LOX in gastric carcinoma was validated by multiple databases and contributed to the poor overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) of stomach adenocarcinoma (STAD) patients. Next, based on the ceRNA hypothesis, the HIF1A-AS2/RP11-366L20.2-miR-29c axis was characterized as the upstream regulatory mechanism of LOX gene overexpression in gastric cancer by combining correlation analysis, expression analysis, and survival analysis. Finally, we illustrated that LOX gene overexpression leads to dismal prognosis of gastric cancer, perhaps through promoting M2 macrophage polarization and tumor immune escape and enhancing drug resistance of tumor cells to chemotherapeutic drugs. Our research demonstrate that LOX may be potentially applied as a novel prognostic marker and targeting inhibition of LOX holds promise as a treatment strategy for gastric cancer.

Identification of hub genes and construction of an mRNA-miRNA-lncRNA network of gastric carcinoma using integrated bioinformatics analysis

Background Gastric carcinoma (GC) is one of the most common cancer globally. Despite its worldwide decline in incidence and mortality over the past decades, gastric cancer still has a poor prognosis. However, the key regulators driving this process and their exact mechanisms have not been thoroughly studied. This study aimed to identify hub genes to improve the prognostic prediction of GC and construct a messenger RNA-microRNA-long non-coding RNA(mRNA-miRNA-lncRNA) regulatory network. Methods The GSE66229 dataset, from the Gene Expression Omnibus (GEO) database, and The Cancer Genome Atlas (TCGA) database were used for the bioinformatic analysis. Differential gene expression analysis methods and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify a common set of differentially co-expressed genes in GC. The genes were validated using samples from TCGA database and further validation using the online tools GEPIA database and Kaplan-Meier(KM) plotter database. Gene set enrichment analysis(GSEA) was used to identify hub genes related to signaling pathways in GC. The RNAInter database and Cytoscape software were used to construct an mRNA-miRNA-lncRNA network. Results A total of 12 genes were identified as the common set of differentially co-expressed genes in GC. After verification of these genes, 3 hub genes, namely CTHRC1, FNDC1, and INHBA, were found to be upregulated in tumor and associated with poor GC patient survival. In addition, an mRNA-miRNA-lncRNA regulatory network was established, which included 12 lncRNAs, 5 miRNAs, and the 3 hub genes. Conclusions In summary, the identification of these hub genes and the establishment of the mRNA-miRNA-lncRNA regulatory network provide new insights into the underlying mechanisms of gastric carcinogenesis. In addition, the identified hub genes, CTHRC1, FNDC1, and INHBA, may serve as novel prognostic biomarkers and therapeutic targets.

CDKN2A Deletion Leading to Hematogenous Metastasis of Human Gastric Carcinoma

IntroductionSomatic copy number deletion (SCND) of CDKN2A gene is the most frequent event in cancer genomes. Whether CDKN2A SCND drives human cancer metastasis is far from clear. Hematogenous metastasis is the main reason of human gastric carcinoma (GC) death. Thus, prediction GC metastasis is eagerly awaited.MethodGC patients (n=408) enrolled in both a cross-sectional and a prospective cohorts were analysed. CDKN2A SCND was detected with a quantitative PCR assay (P16-Light). Association of CDKN2A SCND and GC metastasis was evaluated. Effect of CDKN2A SCND by CRISPR/Cas9 on biological behaviors of cancer cells was also studied.ResultsCDKN2A SCND was detected in 38.9% of GCs from patients (n=234) enrolled in the cross-sectional cohort. Association analysis showed that more CDKN2A SCND was recognized in GCs with hematogenous metastasis than those without (66.7% vs. 35.7%, p=0.014). CDKN2A SCND was detected in 36.8% of baseline pN0M0 GCs from patients (n=174) enrolled in the prospective study, the relationship between CDKN2A SCND and hematogenous metastasis throughout the follow-up period (62.7 months in median) was also significant (66.7% vs. 34.6%, p=0.016). Using CDKN2A SCND as a biomarker for predicting hematogenous metastasis of GCs, the prediction sensitivity and specificity were 66.7% and 65.4%. The results of functional experiments indicated that CDKN2A SCND could obviously downregulate P53 expression that consequently inhibited the apoptosis of MGC803 GC and HEK293T cells. This may account for hematogenous metastasis of GCs by CDKN2A SCND.ConclusionCDKN2A SCND may drive GC metastasis and could be used as a predictor for hematogenous metastasis of GCs.

Relationship between blood group and gastric carcinoma in Erbil city: A case-control study

Background and objective: Gastric carcinoma can be caused by the interaction between environmental factors and genetic variations. The relationship between ABO blood groups and carcinogenesis or progression of human tumors has been reported by many investigations. This study aimed to understand the correlation between ABO blood groups and the risk of developing gastric carcinoma. Methods: This case-control study included the ABO blood group and rhesus system of 92 patients diagnosed with gastric carcinoma at Erbil city from 2017 to 2019. Informed consent was obtained from all patients. As a control, the blood group from 260 healthy blood donors was collected from Erbil blood bank. Results: Of 92 patients, 58.7% were males, and 41.3% were females. The mean age was 62 (28 - 97) years. Regarding the type of gastric carcinoma, 58.7% were intestinal, and 41.3% were diffuse type. Blood group and rhesus system of patients and control were compared. Blood group O was 47.8% in cases versus 40.8% in control and 42.6% in all participants, followed by blood group A (31.5% of gastric carcinoma patients and 26.5% of control with a total of 27.8% of all participants). Regarding the Rhesus system, 92.4% of cases were Rh+, and 7.6% were Rh- compared with 92.9% Rh+and 7.1% Rh- in control. None of them was statistically significant. Conclusion: There was no statistically significant association between blood groups and gastric carcinoma, although blood group O was more common, followed by A. Keywords: Gastric carcinoma; ABO blood group; Erbil.

Case Report on Gastric Carcinoma

Introduction: Gastric cancer or stomach cancer is an any malignant tumor arising from the region extending between the gastroesophageal (GE) junction and the pylorus. The incidence and mortality of gastric cancer have been declining in most developed countries. The age-adjusted risk fell 5% from 1985-1990.Clinical. Findings: Abdominal pain in an region, weakness and loss of appetite from 50 days, pain in lower limb from one month, nausea and vomiting, history of passage of black color stool (for two days, 50 days back), loss of weight five kg in last one month. Diagnostic Evaluation: Hb - 11.2 gm/dl Decreased , RBC 4.17cumm,CBC MCH- 22.6 Pico gm (decrease), Platelet -1.2 lakhs / cumm (decrease), Eosinophil- 9 % (increase )Monocytes-2% (decrease), KFT- sodium – 132 meq/L (decrease) LFT -bilirubin (conjugated) – 0.30 gm %(decrease)Bilirubin (unconjugated ) 0.33 gm %{ decrease}, CT scan, MRI, Upper GI endoscopy - showed abnormal mass ,Endoscopic ultrasound lesion as small as 2-3 mm in diameter, USG CECT Abdomen Report- showed enhancing wall thickening Involving body of gastric without obvious perigastric extension Or significant, consistent with gastric carcinoma. Histopathology report of gastrectomy specimen showed poorly Differentiated adenocarcinoma gastric­ mixed type – pT4a N1 M0. Therapeutic Interventions: Inf. Metrogyl 500 mg TDS, Inj. Amikacin 500 mg OD, Inj. Pantop 40 mg BD , Inj. Piptaz in 100ml NS 4.5 mg TDS, Inj. Levofloxacin 500 mg OD, Tab. Telma 40 mg OD, Inj. PCM in 100ml NS 500 mg TDS, Chemotherapy and Radiation therapy was also Done. Outcome: After treatment, the patient show improvement. His abdominal pain , nausea and vomiting , pain in lower limb were relieved and After all pharmacological, surgical and medical intervention , patient is now in stables condition his mental and it physical condition is improving and laboratory value are in normal range, and he is able to do his daily activities. Conclusion: My patient was admit in surgery Ward No- 28 , AVBRH with a known case of Gastric carcinoma and he had complaint of abdominal pain, nausea and vomiting ,pain in lower limb , weakness, black color stool and loss of appetite. After getting appropriate treatment his condition was improve.

Advances in the Aetiology & Endoscopic Detection and Management of Early Gastric Cancer

The mortality rates of gastric carcinoma remain high, despite the progress in research and development in disease mechanisms and treatment. Therefore, recognition of gastric precancerous lesions and early neoplasia is crucial. Two subtypes of sporadic gastric cancer have been recognized: cardia subtype and non-cardia (distal) subtype, the latter being more frequent and largely associated with infection of Helicobacter pylori, a class I carcinogen. Helicobacter pylori initiates the widely accepted Correa cascade, describing a stepwise progression through precursor lesions from chronic inflammation to gastric atrophy, gastric intestinal metaplasia and neoplasia. Our knowledge on He-licobacter pylori is still limited, and multiple questions in the context of its contribution to the pathogenesis of gastric neoplasia are yet to be answered. Awareness and recognition of gastric atrophy and intestinal metaplasia on high-definition white-light endoscopy, image-enhanced endoscopy and magnification endoscopy, in combination with histology from the biopsies taken accurately according to the protocol, are crucial to guiding the management. Standard indications for endoscopic resections (endoscopic mucosal resection and endoscopic submucosal dissection) of gastric dysplasia and intestinal type of gastric carcinoma have been recommended by multiple societies. Endoscopic evaluation and surveillance should be offered to individuals with an inherited predisposition to gastric carcinoma.