scholarly journals Identification of cluster of differentiation molecule-associated microRNAs as potential therapeutic targets for gastrointestinal cancer immunotherapy

2021 ◽  
pp. 172460082110054
Author(s):  
Hanyu Zhang ◽  
Mingxing Li ◽  
Parham Jabbarzadeh Kaboli ◽  
Huijiao Ji ◽  
Fukuan Du ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Gastrointestinal Cancer ◽  
Therapeutic Targets ◽  
Microrna Expression ◽  
The Cancer Genome Atlas ◽  
Gastrointestinal Cancers ◽  
Almost All ◽  
Cluster Of Differentiation

Background: Cluster of differentiation molecules are markers of immune cells that have been identified as a potential immunotherapeutic target for cancer treatment. MicroRNAs are small non-coding RNAs that act as tumor suppressors or oncogenes whose importance in diagnosis, prognosis, and treatment of gastric and colorectal cancers has been widely reported. However, their association with cluster of differentiation molecules in gastrointestinal cancers has not been well studied. Therefore, our study aimed to analyze the relationship between microRNAs and cluster of differentiation molecules in gastrointestinal cancers, and to identify cluster of differentiation molecule-associated microRNAs as prognostic biomarkers for gastrointestinal cancer patients. Methods: Targetscan, Starbase, DIANA microT, and miRDB were used to investigate microRNA profiles that might be correlated with cluster of differentiation molecules in gastrointestinal cancers. Moreover, The Cancer Genome Atlas data analysis was used to investigate the association between cluster of differentiation molecules and microRNA expression in patients with gastric, colon, rectal, pancreatic, and esophageal cancers. The Kaplan–Meier plotter was used to identify the association between overall survival and cluster of differentiation molecule-associated microRNA expression in gastrointestinal cancer patients. Results: miR-200a, miR-559, and miR-1236 were negatively associated with CD86, CD81, and CD160, respectively, in almost all types of gastrointestinal cancers, which were further verified in the in vitro studies by transfecting microRNA mimics in gastric cancer, colon cancer, pancreatic, and esophageal cell lines. Conclusion: Our study showed that miR-200a, miR-1236, and miR-559 are identified as cluster of differentiation-associated microRNAs in gastrointestinal cancers, providing a novel perspective to identify new therapeutic targets for cancer immunotherapy in gastrointestinal cancer patients.

scholarly journals Epigenetic Alterations in Oesophageal Cancer: Expression and Role of the Involved Enzymes

2020 ◽  
Vol 21 (10) ◽  
pp. 3522
Author(s):  
Nair Lopes ◽  
Margareta P. Correia ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Oesophageal Cancer ◽  
Therapeutic Targets ◽  
Normal Mucosa ◽  
The Cancer Genome Atlas ◽  
Epigenetic Alterations ◽  
Life Threatening ◽  
Cancer Genome Atlas ◽  
In Vitro Data

Oesophageal cancer is a life-threatening disease, accounting for high mortality rates. The poor prognosis of this malignancy is mostly due to late diagnosis and lack of effective therapies for advanced disease. Epigenetic alterations may constitute novel and attractive therapeutic targets, owing to their ubiquity in cancer and their reversible nature. Herein, we offer an overview of the most important studies which compared differences in expression of enzymes that mediate epigenetic alterations between oesophageal cancer and normal mucosa, as well as in vitro data addressing the role of these genes/proteins in oesophageal cancer. Furthermore, The Cancer Genome Atlas database was interrogated for the correlation between expression of these epigenetic markers and standard clinicopathological features. We concluded that most epigenetic players studied thus far are overexpressed in tumours compared to normal tissue. Furthermore, functional assays suggest an oncogenic role for most of those enzymes, supporting their potential as therapeutic targets in oesophageal cancer.

The sensitivity and specifity of DR-70 as a tumor marker for gastrointestinal cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22061-e22061
Author(s):  
Burcak Erkol ◽  
Basak Bala Oven ◽  
Vedat Bayoglu ◽  
Nurcan Paker ◽  
Koray Kochan ◽  
...  
Keyword(s):  
Tumor Marker ◽  
Cancer Patients ◽  
Sensitivity And Specificity ◽  
Gastrointestinal Cancer ◽  
Degradation Products ◽  
Early Stage ◽  
Gastrointestinal Cancers ◽  
Predictive Values ◽  
Significant Difference

e22061 Background: There is a great need to detect gastrointestinal cancers at an early stage, reduce morbidity and mortality. CEA and CA 19-9 are widely used serological markers for gastrointestinal cancers during follow-up. Their utility are limited because of their low sensitivity. In this study, a novel tumor marker DR-70 is evaluated for the sensitivity and specificity, relationship between clinical parameters and compared with CEA and CA 19-9. Methods: Blood sera of 101 histologically proven gastrointestinal cancer patients (38 female, 63 male; 42 colon, 25 rectum, 18 stomach, 9 pancreas, 4 esophagus and 3 cholangiocellular carcinomas) and 105 healthy blood donors were included. The TNM stage of the disease and histologic grade was shown. All patients and controls were also tested for CEA and CA 19-9 levels. In DR-70 immunoassay, the fibrin degradation products were quantitatively measured using ELISA DR-70 kits. Results: The median DR-70, CEA and CA19-9 levels were 1.6 µg/mL, 3.05 ng/mL and 22.2 IU/L in cancer patients, they were lower in healthy control 0.5 µg/mL, 0.9 ng/mL, 1.9 IU/L; p < 0.001. While the stage and grade increased, the levels of DR-70, CEA and CA-19-9 (p < 0.05) were increased significantly. DR-70 and CA19-9 values were highest in patients with pancreas, and lowest in rectum cancer, there was no statistically significant difference between tumor localization and CEA levels.The sensitivity, specificity and the cut-off value of DR-70, in patients with malignancy by using ROC analysis were found as 97%, 95% and < 0.75 µg/mL, respectively. The positive and negative predictive values were 95%, and 97% and the efficacy was 96%. Sensitivities of CEA (cut off value 3ng/mL) and CA 19-9 (cut off value 37 U/ml) were 52% and 39% respectively, the specificities were 94% and 99% for CEA and CA 19-9, respectively; sensitivity increased by combined use of both of them. Conclusions: Due to its high sensitivity and specificity, high positive and negative predictive values DR-70 can be used more frequently as a tumor marker for detection of gastrointestinal cancer. It can also be used in tumor progression and treatment follow-up because of positive correlation between DR-70 levels and the tumor stage.

scholarly journals Identification and verification of HCAR3 and INSL5 as new potential therapeutic targets of colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuan Yang ◽  
Wangao Wei ◽  
Shisheng Tan ◽  
Linrui Guo ◽  
Song Qiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Tumor Tissue ◽  
Therapeutic Targets ◽  
The Cancer Genome Atlas ◽  
Pcr Analysis ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Real Time Quantitative Pcr

Abstract Background Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines. Methods A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein–protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro. Results A total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified: CXCL1, HCAR3, CXCL6, CXCL8, CXCL2, CXCL5, PPY, SST, INSL5, and NPY1R. Among these genes, HCAR3 and INSL5 had not previously been explored and were further verified in vitro. Conclusions HCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells. This integrated bioinformatics study presented 10 key hub genes associated with CRC. HCAR3 and INSL5 were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.

scholarly journals Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jessica M. Sierra ◽  
Florencia Secchiari ◽  
Sol Y. Nuñez ◽  
Ximena L. Raffo Iraolagoitia ◽  
Andrea Ziblat ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Nk Cells ◽  
Cancer Patients ◽  
Nk Cell ◽  
The Cancer Genome Atlas ◽  
T Cell Proliferation ◽  
Dependent Manner ◽  
Effector Functions

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.

scholarly journals Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Huan Wang ◽  
Qi Cheng ◽  
Kaikai Chang ◽  
Lingjie Bao ◽  
Xiaofang Yi
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
M2 Macrophage ◽  
Gynecological Malignancy

Ovarian cancer remains the most lethal gynecological malignancy. Ferroptosis, a specialized form of iron-dependent, nonapoptotic cell death, plays a crucial role in various cancers. However, the contribution of ferroptosis to ovarian cancer is poorly understood. Here, we characterized the diagnostic, prognostic, and therapeutic value of ferroptosis-related genes in ovarian cancer by analyzing transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A reliable 10-gene ferroptosis signature (HIC1, ACSF2, MUC1, etc.) for the diagnosis of ovarian cancer was identified. Notably, we constructed and validated a novel prognostic signature including three FRGs: HIC1, LPCAT3, and DUOX1. We also further developed a risk score model based on these three genes which divided ovarian cancer patients into two risk groups. Functional analysis revealed that immune response and immune-related pathways were enriched in the high-risk group. Meanwhile, the tumor microenvironment was distinct between the two groups, with more M2 Macrophage infiltration and higher expression of key immune checkpoint molecules in the high-risk group than in the other group. Low-risk patients exhibited more favorable immunotherapy and chemotherapy responses. We conclude that crosstalk between ferroptosis and immunity may contribute to the worse prognosis of patients in the high-risk group. In particular, HIC1 showed both diagnostic and prognostic value in ovarian cancer. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients.

scholarly journals Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3035
Author(s):  
Alessandra Dall'Acqua ◽  
Michele Bartoletti ◽  
Nastaran Masoudi-Khoram ◽  
Roberto Sorio ◽  
Fabio Puglisi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Therapeutic Targets ◽  
Metastatic Breast ◽  
Molecular Alterations ◽  
Estrogen Receptor Positive ◽  
Cancer Types ◽  
Almost All ◽  
Tumor Types

Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease.

scholarly journals Postoperative Low Molecular Weight Heparin-induced Infection in Gastrointestinal Cancer Patients. A 2-year Single Centre Experience 

Folia Medica ◽  
2020 ◽  
Vol 62 (4) ◽  
pp. 769-776
Author(s):  
Alexandrina Nikova ◽  
Maria Kyriazi ◽  
Helena Michalopoulou ◽  
Melani Demetriou ◽  
Vasilis Tselepidis ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Sample Size ◽  
Cancer Patients ◽  
Gastrointestinal Cancer ◽  
Postoperative Management ◽  
Low Molecular Weight ◽  
Essential Question ◽  
Elastic Stockings

Introduction: Patients with gastrointestinal cancer are at high risk of developing thrombosis and postoperative infection. Antico-agulation therapy for such patients is provided by low molecular weight heparin (LMWH) and elastic stockings. The latter, however, is linked to immunoregulatory activities and immunosuppression in vivo and in vitro. Aim: Therefore, the present study aimed to examine the link between LMWH and infection in patients with gastrointestinal cancer. Materials and methods: The study is a retrospective report of 51 patients operated on at the Second Department of Surgery at Metaxa Cancer Hospital. The sample was divided into groups based on the presence or absence of diabetes and preoperative anticoagu-lation therapy. Afterwards, the data were statistically analysed.&nbsp; Results: The results of the study show a statistically significant correlation between LMWH and infection. Moreover, the risk of infec-tion increases by 13.3% for each day of heparin intake. The theory of this correlation is explained in detail.&nbsp; Conclusions: The findings of the present study raise an essential question about postoperative management of cancer patients. How-ever, the study sample size is rather small so further studies with larger sample size are required to give greater credence to results.

scholarly journals Evaluation of circulating microRNAs as non-invasive biomarkers in the diagnosis of ovarian cancer: a case–control study

2021 ◽  
Author(s):  
Kai Berner ◽  
Marc Hirschfeld ◽  
Daniela Weiß ◽  
Gerta Rücker ◽  
Jasmin Asberger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Microrna Expression ◽  
Urine Samples ◽  
Malignant Diseases ◽  
Liquid Biopsies ◽  
Expression Levels

Abstract Purpose Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150,000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late-stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo. Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative real-time-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed. Results MiR-15a, miR-20a and miR-222 showed expression level alterations extracellularly, whereas miR-125b did intracellularly across the analyzed cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Hypoxia and acidosis showed scarce effects on single miRNA expression levels only. Furthermore, we were able to demonstrate the feasibility to clearly detect the 12 miRNAs in urine samples. In urine, miR-15a was upregulated whereas let-7a was down-regulated in ovarian cancer patients. Conclusion Intracellular, extracellular and urinary microRNA expression alterations emphasize their great potential as biomarkers in liquid biopsies. Especially, miR-15a and let-7a qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients.

scholarly journals Evaluation of Circulating microRNAs as Non-Invasive Biomarkers in the Diagnosis of Ovarian Cancer – A Case-Control Study

2020 ◽  
Author(s):  
Kai Berner ◽  
Marc Hirschfeld ◽  
Daniela Weiß ◽  
Gerta Rücker ◽  
Jasmin Asberger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Microrna Expression ◽  
Urine Samples ◽  
Malignant Diseases ◽  
Liquid Biopsies ◽  
Expression Levels

Abstract Background Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150.000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo.Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative real-time-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed.Results MiR-15a, miR-20a and miR-222 showed expression level alterations extracellularly, whereas miR-125b did intracellularly across the analyzed cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Hypoxia and acidosis showed scarce effects on single miRNA expression levels only. Furthermore, we were able to demonstrate the feasibility to clearly detect the 12 miRNAs in urine samples. In urine, miR-15a was upregulated whereas let-7a was down-regulated in ovarian cancer patients.Conclusion Intracellular, extracellular and urinary micoRNA expression alterations emphasize their great potential as biomarkers in liquid biopsies. Especially miR-15a and let-7a qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients.

scholarly journals Prognostic role of SIRT6 in gastrointestinal cancers: a meta-analysis

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 358-365
Author(s):  
Li Shi ◽  
Ying Wang ◽  
Timothy Bonney Oppong ◽  
Xiaoli Fu ◽  
Haiyan Yang ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gastrointestinal Cancer ◽  
Web Of Science ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Critical Role ◽  
Clinicopathological Parameters ◽  
Gastrointestinal Cancers ◽  
Potential Biomarker

AbstractSirtuin 6 (SIRT6) plays a critical role in the progression and development of gastrointestinal cancers. However, the association between SIRT6 expression and clinicopathological parameters and prognosis in gastrointestinal cancer patients remains inconclusive. Consequently, we conducted this meta-analysis to evaluate the importance of SIRT6 expression in various types of gastrointestinal cancers. PubMed, EMBASE, and Web of Science databases were systematically searched to screen the relevant literature. The reported or estimated hazard ratio (HR) and odds ratio (OR) and their corresponding 95% confidence interval (CI) were pooled to assess the strength of the association. Nine studies involving 867 patients were included in the meta-analysis. Overall analysis showed that high SIRT6 expression was related to better overall survival in gastrointestinal cancers (HR = 0.62, 95% CI = 0.47–0.82). High SIRT6 expression was also related to a favorable tumor node metastasis (TNM) stage (OR = 0.44, 95% CI = 0.28–0.70) among gastrointestinal cancer patients. Our meta-analysis revealed that high SIRT6 expression might be a potential biomarker predicting better prognosis in gastrointestinal cancers, which may offer options for gastrointestinal cancer treatment.

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