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Since the 1956 hypothesis of Otto Warburg, aerobic glycolysis has been recognized as a metabolic hallmark of cancer. Because methylglyoxal (MG) is a naturally occurring waste metabolite of glycolysis, we measured blood levels of this molecule in colon cancer-bearing rats. To compare the blood levels of free MG in cancerous and healthy animals,the present study used a dedicated tumor graft model consisting of the subcutaneous administration in syngenic BD-IX rats of a tumorigenic cell clone (PROb) and another non-tumorigenic clone (REGb) derived from the same tumor. Rats grafted with the PROb growing tumor cell clone exhibited a statistically significant increase in free MG blood levels (P=0.003), whereas rats transplanted with the REGb non-growing tumor cell clone exhibited normal MG values. The present study (first of three parts) suggests that cancer cells can produce and release free MG at higher levels than normal cells, making MG a putative novel metabolic biomarker of cancer. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that members of the brain-expressed X-linked (BEX) family participate in a wide range of biological functions in normal and tumor tissues. However, their role and clinical significance in lung adenocarcinoma (LUAD) remains unclear. The present study investigated The Cancer Genome Atlas data and revealed that the BEX family was downregulated in LUAD tissues compared with adjacent non-cancerous tissues. Additionally, analysis of LUAD cohorts from the Oncomine database revealed similar results. Furthermore, the expression of BEX members was significantly decreased in several LUAD cell lines compared with normal lung epithelial cells in vitro. The aforementioned data mining and in vitro results suggested that the BEX family may be involved in the development of LUAD. Furthermore, receiver operating characteristic curve analysis revealed that BEX members exhibited high sensitivity and specificity for the diagnosis of patients with LUAD. The low expression levels of BEX1, BEX4 and BEX5 were associated with certain pathologic features, particularly in advanced LUAD. Survival analysis demonstrated that BEX members, particularly BEX4, were involved in the prognosis of patients with LUAD at early and late clinical stages. The results obtained in the current study suggested that BEX members may serve as potential tumor biomarkers for the diagnosis and prognosis of patients with LUAD. [ABSTRACT FROM AUTHOR]

Compared with linear RNA, circular RNAs (circRNAs) form a covalently closed circular continuous loop and are highly conserved, stable and tissue-specific. In recent years, circRNAs received considerable attention in the diagnosis, classification, treatment and prognosis of hematological tumors. circRNAs function as microRNA sponges and competitive endogenous RNAs that play an essential role in the translation, regulation and interaction of proteins. The present review discussed the fundamental properties and functions of circRNAs and the latest advancements in the context of circRNAs in the clinical research of hematological malignancies, namely acute and chronic myeloid leukemia, and chronic lymphocytic leukemia. circRNAs show potential in the diagnosis and prognosis of various diseases and can be used as therapeutic targets and biomarkers for disease. [ABSTRACT FROM AUTHOR]

Integrin signaling may modulate several different functions involved in cell migration, invasion, proliferation and motility, and is a potential candidate biomarker for oral cancer. In the present study, a total of four integrin genes were evaluated as potential biomarkers of oral squamous cell carcinoma (OSCC). Gene expression was determined using the reverse transcription‑quantitative polymerase chain reaction in 55 OSCC and 55 matched normal oral tissues. The performance of individual and combined biomarkers was analyzed by receiver operating characteristic (ROC) analysis based on the relative mRNA expression (OSCC vs. matched oral tissue from the tumor‑free margin), which was calculated using the ΔΔCq value (ΔCq of OSCC‑ΔCq of oral tissue from the tumor‑free margin of the same patient). In the individual ROC analysis, the areas under the ROC curve (AUCs) of relative mRNA expression (ΔΔCq) of integrin subunit α3 (ITGA3), integrin subunit α5 (ITGA5), integrin subunit β1 (ITGB1) and integrin subunit β6 (ITGB6) in all tumor locations were 0.724, 0.698, 0.640 and 0.657, respectively. For locations 2 (tongue/mouth part) and 3 (edentulous ridge), their individual AUC values were 0.840, 0.765, 0.725 and 0.763, respectively. In the cumulative ROC analysis, ITGA3, ITGA5 and ITGB1 genes exhibited the highest combined AUC values (0.809 and 0.871 for all locations and locations 2 and 3 combined, respectively) compared with other biomarker combinations. In conclusion, the results of the present study identified that higher mRNA expressions of ITGA3, ITGA5, ITGB1 and ITGB6 genes are suitable for OSCC diagnosis biomarkers. Cumulative ROC analysis indicated an improved overall performance compared with the best individual integrin biomarker of OSCC. [ABSTRACT FROM AUTHOR]

Serine proteinase inhibitor, clade E member 2 (SERPINE2), also known as protease nexin-1 (PN-1), is a member of the serpin family. Despite several reported roles of SERPINE2 in tumor development the histological distribution of SERPINE2 and its expression levels in a large variety of tumors remains unclear. Through expressed sequence tag database analysis, immunohistochemical staining of tissue microarrays and a literature review, it was revealed that SERPINE2 expression varied according to growth stages and tissue types. SERPINE2 is differentially expressed in a number of tumors and their normal tissue counterparts. SERPINE2 is identified most abundantly in adenocarcinomas. SERPINE2 serves diverse roles in a variety of tumors and therefore may serve as a promising biomarker for tumor diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common types of malignant tumor in the world and occurs through a multi-step process resulting from the accumulation of genetic and epigenetic alterations of the genome. Although the molecular mechanisms of the pathogenesis of CRC remain unclear, the inactivation of tumor suppressor genes (TSGs) through promoter methylation serves an important role. Aberrant methylation is a well-defined marker of CRC. At present, the epigenetic silencing of protocadherin 10 (PCDH10) has been identified as an important TSG with key roles in colorectal carcinogenesis, invasion and metastasis as a frequent and early event. Advances in gene methylation detection in tumor tissues and body fluids have led to the development of non-invasive screening methods for CRC. The present study aimed to review the epigenetic alteration of PCDH10 in CRC development, and the potential of PCDH10 to be a non-invasive biomarker for CRC. [ABSTRACT FROM AUTHOR]

The role of microRNAs (miRs) as possible biomarkers and therapy targets has been extensively investigated in a number of types of cancer. However, the aberrant expression of miRs in laryngeal squamous cell carcinoma (LSCC), particularly during the progression of the disease, is poorly understood. In the present study, the role of miRs as possible novel early pre-diagnostic biomarkers of LSCC was investigated. TaqMan probe stem-loop quantitative polymerase chain reaction was utilized to accurately measure the amount of miR-148a and miR-375 in clinical samples of mild dysplasia, moderate dysplasia, severe dysplasia, cancer in situ, laryngeal cancer and normal epithelial controls. The application of miR-148a and miR-375 as potential predictive biomarkers for early diagnosis of LSCC was analyzed. The results of the present study suggested that miR-148a and miR-375 were significantly upregulated in LSCC tissues, and increased expression of miR-375 was associated with a more aggressive phenotype of LSCC. Additional investigation revealed that miR-148a and miR-375 increased during different dysplasia stages of LSCC carcinogenesis, and high-level expression of miR-148a or miR-375 in patients with laryngeal dysplasia may predict subsequent malignant transformation. miR-148a and miR-375 were significantly upregulated during LSCC carcinogenesis and may serve as possible predictive biomarkers for early diagnosis of LSCC. [ABSTRACT FROM AUTHOR]

Sperm-associated antigen 6 (SPAG6) is a newly identified cancer-testis antigen that has been revealed to contribute to the occurrence and development of various types of human cancer, such as ovarian, bladder, breast and lung cancer. However, to the best of our knowledge, the expression levels of SPAG6 in breakpoint cluster region (BCR)/ABL1-negative myeloproliferative neoplasms (MPNs) have not been investigated previously. Using reverse transcription-quantitative PCR and different tissue staining techniques, the present study revealed that SPAG6 was expressed by MPN cells, both at the mRNA and protein levels, and that nucleated erythroid precursors and megakaryocytes expressed the highest levels of SPAG6. In addition, SPAG6, which is known as a microtubule-associated protein, was found to exhibit nucleic, cytoplasmic or both cytoplasmic and nucleic subcellular localization patterns within the same patient or cell type; however, it did not always co-localize with β-tubulin. Furthermore, SPAG6 expression was revealed to be associated with fewer splenomegaly [P=0.015 for polycythemia vera (PV) and essential thrombocythemia (ET); and P=0.012 for primary myelofibrosis (PMF)] and myelofibrosis events (P=0.014 for PV and ET; and P=0.004 for PMF). In patients with PMF, upregulated expression levels of SPAG6 were also found to be associated with lower white blood cell counts (P=0.042) and lactate dehydrogenase levels (P=0.012), and higher hemoglobin levels (P=0.031) and platelet counts (P=0.025). In addition, the receiver operating characteristic curve analysis indicated that SPAG6 may be a potential biomarker for distinguishing MPN cases from healthy individuals. In conclusion, to the best of our knowledge, the present study is the first to report that aberrant SPAG6 expression may affect the disease phenotype and serve as a tumor biomarker in BCR/ABL1-negative MPNs. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB), the most common intraocular malignancy, typically occurs in pediatric patients under the age of 6 years. The present study aimed to explore the long noncoding RNA (lncRNA) expression profile in RB and identify novel lncRNA biomarkers to facilitate the investigation of molecular mechanisms of RB and improve clinical therapy. Raw microarray data for the comparison of gene expression between three RB and three adjacent normal tissue samples were downloaded from Gene Expression Omnibus (dataset no. GSE111168). After identification of differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) in RB, functional enrichment analyses and a DEL-DEM weighted correlation network analysis were performed. A total of 3,915 DELs (1,774 upregulated and 2,141 downregulated) and 3,715 DEMs (1,492 upregulated and 2,223 downregulated) were identified in RB. The DEL-targeted DEMs were highly enriched by genes involved in hexose transport, muscle tissue morphogenesis, the stereocilium membrane, endothelin B receptor binding and γ-filamin/ABP-L, α-actinin and telethonin binding protein of the Z-disc binding. Furthermore, associations of the DELs and DEMs with several pathways were determined, including PI3K/AKT, Hippo and cancer signaling, as well as extracellular matrix-receptor interaction pathways. Coexpression network analysis revealed that the top three DELs, lnc-DAZ1-161, lnc-HDAC7-21 and lnc-OR52A1-55, formed coexpression modules with 181, 156 and 210 DEMs, respectively. In addition, the top three DEMs, namely EIF1AY, GSTM1 and NLRP11, formed coexpression modules with 33, 50 and 41 DELs, respectively. Validation using reverse transcription-quantitative PCR indicated that the expression of representative lncRNAs (lnc-DAZ1-161 and lnc-HDAC7-21) in RB cells in vitro was consistent with that in RB tissues in the database, while the expression of lnc-OR52A1-55 was not consistent with the database. These results suggested that the aberrant lncRNA expression profile in RB is related to the differential regulation of numerous physiological and pathological processes. The lncRNA and mRNA profiles in RB identified may provide novel targets for the investigation of its molecular mechanisms and thus lead to improvements in clinical therapy for RB. [ABSTRACT FROM AUTHOR]