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Frontiers in Immunology 2022Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in...
BACKGROUND
Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction.
METHODS
By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes.
RESULTS
The results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers.
CONCLUSION
Through pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.
Topics: Adenocarcinoma; Biomarkers, Tumor; Glypicans; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 35345673
DOI: 10.3389/fimmu.2022.857308 -
Biomedicine & Pharmacotherapy =... Feb 2021Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nt and lack a protein-coding ability. They regulate gene expression by... (Review)
Review
Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nt and lack a protein-coding ability. They regulate gene expression by interacting with protein, RNA, and DNA. Their function is closely related to their subcellular localization. In the nucleus, lncRNAs regulate gene expression at the epigenetic and transcriptional levels, and in the cytoplasm, they regulate gene expression at the post-transcriptional and translational levels. Abnormalities in lncRNAs have been confirmed to exhibit tumor suppressor or carcinogenic effects and play an important role in the development of tumors. In particular, the lung cancer-related transcript 1 (LUCAT1) located in the antisense strand of the q14.3 region of chromosome 5 was first discovered in smoking-related lung cancer. Increasing evidence have showed that LUCAT1 is involved in breast cancer, ovarian cancer, thyroid cancer, renal cell carcinoma. It is highly expressed in liver cancer and other malignant tumors and has been confirmed to be induce various malignant tumors. It regulates tumor proliferation, invasion, and migration via various mechanisms and is related to the clinicopathological characteristics of tumor patients. Thus, LUCAT1 is a potential prognostic biological marker and therapeutic target for cancer. This article reviews its expression, function, and molecular mechanism in various malignant tumors.
Topics: Animals; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; RNA, Long Noncoding; Signal Transduction
PubMed: 33360049
DOI: 10.1016/j.biopha.2020.111158 -
International Journal of Molecular... Jul 2022Gastric cancer (GC)-a common tumor that affects humans worldwide-is highly malignant with a poor prognosis. GC is frequently not diagnosed until a relatively advanced... (Review)
Review
Gastric cancer (GC)-a common tumor that affects humans worldwide-is highly malignant with a poor prognosis. GC is frequently not diagnosed until a relatively advanced stage. Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality. Minimally invasive methods are needed to establish a diagnosis or monitoring the response to treatment of gastric cancer. Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for the risk group or for population-wide based screening programs, The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of gastric cancer. Here we review the available literature on plasma classical tumor markers, circulating free microRNAs (cfmiRNAs), circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs), autoantibodies against tumor associated antigens (TAAs), and circulating extracellular vesicles (EVs) for diagnosis and monitoring of gastric cancer. This review summarizes the present status and approaches for these biomarkers, which could be potentially used for early diagnosis and accurate prediction of therapeutic approaches. We also discuss the future perspective and challenges in the search for new biomarkers of gastric cancer.
Topics: Biomarkers, Tumor; Early Detection of Cancer; Humans; MicroRNAs; Neoplastic Cells, Circulating; Stomach Neoplasms
PubMed: 35886934
DOI: 10.3390/ijms23147588 -
Modern Pathology : An Official Journal... Apr 2021Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen... (Comparative Study)
Comparative Study
Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
Topics: Biomarkers, Tumor; Carcinoma; Databases, Genetic; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Predictive Value of Tests; Repressor Proteins; Reproducibility of Results; Tissue Array Analysis; Triple Negative Breast Neoplasms
PubMed: 33011748
DOI: 10.1038/s41379-020-00692-8 -
Cell Communication and Signaling : CCS Feb 2020Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the... (Review)
Review
Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the widespread occurrence of chemoresistance, which emphasizes the need to discover and develop new methods to treat this disease. Signal transducer and activator of transcription 3 (STAT3) is an early tumor diagnostic marker and is known to promote breast cancer malignancy. Recent clinical and preclinical data indicate the involvement of overexpressed and constitutively activated STAT3 in the progression, proliferation, metastasis and chemoresistance of breast cancer. Moreover, new pathways comprised of upstream regulators and downstream targets of STAT3 have been discovered. In addition, small molecule inhibitors targeting STAT3 activation have been found to be efficient for therapeutic treatment of breast cancer. This systematic review discusses the advances in the discovery of the STAT3 pathways and drugs targeting STAT3 in breast cancer. Video abstract.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Drug Resistance, Neoplasm; Female; Humans; STAT3 Transcription Factor; Signal Transduction
PubMed: 32111215
DOI: 10.1186/s12964-020-0527-z -
World Journal of Gastroenterology Jan 2022Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other... (Review)
Review
Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; alpha-Fetoproteins
PubMed: 35110946
DOI: 10.3748/wjg.v28.i2.216 -
The Journal of Clinical Investigation Jun 2022Cancer cells shed naked DNA molecules into the circulation. This circulating tumor DNA (ctDNA) has become the predominant analyte for liquid biopsies to understand the... (Review)
Review
Cancer cells shed naked DNA molecules into the circulation. This circulating tumor DNA (ctDNA) has become the predominant analyte for liquid biopsies to understand the mutational landscape of cancer. Coupled with next-generation sequencing, ctDNA can serve as an alternative substrate to tumor tissues for mutation detection and companion diagnostic purposes. In fact, recent advances in precision medicine have rapidly enabled the use of ctDNA to guide treatment decisions for predicting response and resistance to targeted therapies and immunotherapies. An advantage of using ctDNA over conventional tissue biopsies is the relatively noninvasive approach of obtaining peripheral blood, allowing for simple repeated and serial assessments. Most current clinical practice using ctDNA has endeavored to identify druggable and resistance mutations for guiding systemic therapy decisions, albeit mostly in metastatic disease. However, newer research is evaluating potential for ctDNA as a marker of minimal residual disease in the curative setting and as a useful screening tool to detect cancer in the general population. Here we review the history of ctDNA and liquid biopsies, technologies to detect ctDNA, and some of the current challenges and limitations in using ctDNA as a marker of minimal residual disease and as a general blood-based cancer screening tool. We also discuss the need to develop rigorous clinical studies to prove the clinical utility of ctDNA for future applications in oncology.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Humans; Liquid Biopsy; Mutation; Neoplasm, Residual; Precision Medicine
PubMed: 35703177
DOI: 10.1172/JCI154941 -
Biomedicine & Pharmacotherapy =... Jan 2022Gastric cancer (GC) is the world's second-leading cause of cancer-related mortality, continuing to make it a serious healthcare concern. Even though the prevalence of GC...
BACKGROUND
Gastric cancer (GC) is the world's second-leading cause of cancer-related mortality, continuing to make it a serious healthcare concern. Even though the prevalence of GC reduces, the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers to diagnose early GC and predict chemosensitivity and recurrence.
METHODS AND MATERIAL
We integrated the gene expression patterns of gastric cancers from four RNAseq datasets (GSE113255, GSE142000, GSE118897, and GSE130823) from Gene Expression Omnibus (GEO) database to recognize differentially expressed genes (DEGs) between normal and GC samples. A gene co-expression network was built using weighted co-expression network analysis (WGCNA). Furthermore, RT-qPCR was performed to validate the in silico results.
RESULTS
The red modules in GSE113255, Turquoise in GSE142000, Brown in GSE118897, and the green-yellow module in GSE130823 datasets were found to be highly correlated with the anatomical site of GC. ITGAX, CCL14, ADHFE1, and HOXB13) as the hub gene are differentially expressed in tumor and non-tumor gastric tissues in this study. RT-qPCR demonstrated a high level of the expression of this gene.
CONCLUSION
The expression levels of ITGAX, CCL14, ADHFE1, and HOXB13 in GC tumor tissues are considerably greater than in adjacent normal tissues. Systems biology approaches identified that these genes could be possible GC marker genes, providing ideas for other experimental studies in the future.
Topics: Alcohol Oxidoreductases; Biomarkers, Tumor; Chemokines, CC; Computational Biology; Early Detection of Cancer; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Homeodomain Proteins; Humans; Mitochondrial Proteins; Prognosis; Stomach Neoplasms
PubMed: 34864309
DOI: 10.1016/j.biopha.2021.112477 -
Frontiers in Immunology 2021Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple...
Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although increasing evidence supports a vital role for TREM2 in tumorigenesis of some cancers, no systematic pan-cancer analysis of TREM2 is available. Thus, we aimed to explore the prognostic value, and investigate the potential immunological functions, of TREM2 across 33 cancer types. Based on datasets from The Cancer Genome Atlas, and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and Human Protein Atlas, we employed an array of bioinformatics methods to explore the potential oncogenic roles of TREM2, including analyzing the relationship between TREM2 and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration of different tumors. The results show that TREM2 is highly expressed in most cancers, but present at low levels in lung cancer. Further, TREM2 is positively or negatively associated with prognosis in different cancers. Additionally, TREM2 expression was associated with TMB and MSI in 12 cancer types, while in 20 types of cancer, there was a correlation between TREM2 expression and DNA methylation. Six tumors, including breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, were screened out for further study, which demonstrated that TREM2 gene expression was negatively correlated with infiltration levels of most immune cells, but positively correlated with infiltration levels of M1 and M2 macrophages. Moreover, correlation with TREM2 expression differed according to T cell subtype. Our study reveals that TREM2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.
Topics: Biomarkers, Tumor; DNA Methylation; DNA Repair; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Membrane Glycoproteins; Microsatellite Instability; Mutation; Neoplasms; Phenotype; Prognosis; Receptors, Immunologic; Tumor Microenvironment
PubMed: 33679809
DOI: 10.3389/fimmu.2021.646523 -
Biochimica Et Biophysica Acta. Reviews... Dec 2021The role of conventional serum tumor marker, carbohydrate antigen 72-4 (CA72-4), in assisting diagnosis, monitoring dynamic progression, and evaluating the prognosis of... (Review)
Review
The role of conventional serum tumor marker, carbohydrate antigen 72-4 (CA72-4), in assisting diagnosis, monitoring dynamic progression, and evaluating the prognosis of gastric cancer (GC) should not be ignored, especially in the Chinese population. Even though CA72-4 has been used in clinical practice for decades, its modest positivity rate, sensitivity, and specificity did not meet the high demand of the clinical application. However, over the years, some progress in the functions of CA72-4 has been achieved, suggesting that CA72-4 can still be considered a promising marker in oncology. As a biomarker, CA72-4 can achieve improved sensitivity (SEN) and specificity (SPE) when combined with other biomarkers, selecting suitable reference values, improving detection techniques, and identifying the risk threshold. As a predictor, elevated serum CA72-4 levels were found to be significantly associated with prognostic risk factors, further assessing therapeutic validity and resectability. Recently, an effective method to reduce the toxicity of CA72-4 targeted therapy has been developed. Moreover, CA72-4 could induce novel aptamers to react with tumor cells and enhance the efficacy of trastuzumab in HER2-positive GC. Therefore, in this review, we discuss the most recent application of CA72-4 in the diagnosis, prognosis, and treatment of GC.
Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Humans; Prognosis; Stomach Neoplasms
PubMed: 34656687
DOI: 10.1016/j.bbcan.2021.188634