To evaluate the diagnostic value of combining the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) or lymphocyte-monocyte ratio (LMR) with carcinoembryonic antigen (CEA) in patients with colorectal cancer (CRC). Patients and methods: The diagnostic performance of inflammatory makers and CEA was evaluated in cohort 1 (664 patients with CRC, 336 patients with colorectal polyps and 664 healthy controls) and validated in cohort 2 (87 patients with CRC and 87 healthy controls) by using receiver operating characteristic curve analysis. Results: In cohort 1, the NLR, PLR and CEA levels were significantly higher, while the LMR was markedly lower in patients with CRC than in healthy controls. The PLR and LMR were significantly associated with invasion depth and lymph node metastasis. Moreover, significant differences in the PLR and LMR were observed between patients with stage I/II CRC and healthy or polyp controls and those with stage III/IV CRC. Using the NLR, PLR or LMR with CEA resulted in a significantly larger area under the curve (AUC) than any of them used alone. Combining the PLR and LMR with CEA exhibited the best diagnostic value for CRC (AUC=0.892). The AUCs of this combination were 0.864 and 0.783 for distinguishing stage I/II CRC from healthy and polyp controls, respectively. When we used the same cutoff values to assess the diagnostic ability of these markers in cohort 2, similar results were observed, and the PLR, LMR and CEA combination also showed the highest accuracy (AUC=0.936). Conclusion: Combining inflammatory cell ratios with CEA could improve the diagnostic efficacy for CRC patients. The combination of the PLR and LMR with CEA might be a valuable indicator in the early detection and monitoring of CRC patients.
Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database. Through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information of 876 GC patients, we also investigated the prognostic values of ALDH1 isoenzymes in GC patients. It was found that when compared with normal tissues, ALDH1A1 mRNA expression was downregulated, whereas ALDH1A3 and ALDH1B1 were upregulated in GC patients. In survival analyses, high ALDH1A1 and ALDH1B1 expressions were associated with better overall survival (OS) in all GC patients. In addition, high transcription activity of ALDH1A1 predicted better OS in gastric intestinal type adenocarcinoma, but not in diffuse gastric adenocarcinoma. GC patients with high mRNA level of ALDH1B1 showed better OS in gastric intestinal type, and worse OS in diffuse type. Oppositely, high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in GC patients, suggesting that these isoenzymes might be responsible mainly for the ALDH1 activities in GC. These data provides ALDH1A2, ALDH1A3 and ALDH1L1 as excellent potential targets for individualized treatment of GC patients.
DNA N6-methyladenosine (6mA) is a novel epigenetic signaling modification in humans and has been implicated in the progression and tumorigenesis of several cancers. However, the function and mechanism of 6mA in breast cancer (BC), the most common cancer among women, are unclear. Here, we found that decreases in N6AMT1 correlated with the extent of 6mA in clinical BC tissues and predicted a worse survival of BC patients. Functionally, knockdown of N6AMT1 markedly reduced 6mA in DNA and promoted colony formation and migration of BC cells, whereas overexpression of N6AMT1 had the opposite effect. Moreover, silencing of N6AMT1 reduced 6mA modification and enhanced the growth of BC cells in vitro and tumors in vivo. 6mA immunoprecipitation sequencing (6mA-IP-seq), RNA-seq, 6mA-IP-PCR, and bioinformatics analysis indicated that N6AMT1 was a functional methyltransferase for genomic 6mA DNA modifications and related to gene transcriptional activity. Critical negative regulators of the cell cycle, such as RB1, P21, REST, and TP53 were identified as targets of N6AMT1 in BC. These results suggest N6AMT1 enhances DNA 6mA levels to repress tumor progression via transcriptional regulation of cell cycle inhibitors.
BackgroundOur previous study has shown that cadmium (Cd) exposure is not only a risk factor for nasopharyngeal carcinoma (NPC), but also correlated with the clinical stage and lymph node metastasis. However, the underlying molecular events of Cd involved in NPC progression remain to be elucidated.PurposeThe objective of this study was to decipher how Cd impacts the malignant phenotypes of NPC cells.MethodsNPC cell lines CNE-1 and CNE-2 were continuously exposed with 1 μM Cd chloride for 10 weeks, designating as chronic Cd treated NPC cells (CCT-NPC). MTT assay, colony formation assay and xenograft tumor growth were used to assess cell viability in vitro and in vivo. Transwell assays were performed to detect cell invasion and migration. The protein levels of E-cadherin, N-cadherin, Vimentin as well as β-catenin and casein kinase 1α(CK1α) were measured by Western blot. Immunofluorescence staining was used to observe the distribution of filament actin (F-actin), β-catenin and CK1α. The mRNA levels of downstream target genes of β-catenin were detected by RT-PCR. Wnt/β-catenin signaling activity was assessed by TOPFlash/FOPFlash dual luciferase report system. MS-PCR was used to detect the methylation status of CK1α. Finally, the activation of Wnt/β-catenin pathway and cell biological properties were examined following treatment of CCT-NPC cells with 5-aza-2-deoxy-cytidine(5-aza-CdR).ResultsCCT-NPC cells showed an increase in cell proliferation, colony formation, invasion and migration compared to the parental cells. Cd also induced cytoskeleton reorganization and epithelial-to-mesenchymal transition. Upregulation and nuclear translocation of β-catenin and increased luciferase activity accompanied with transcription of downstream target genes were found in CCT-NPC cells. Treatment of CCT-CNE1 cells with 5-aza-CdR could reverse the hypermethylation of CK1α and attenuate the cell malignancy.ConclusionThese results support a role for chronic Cd exposure as a driving force for the malignant progression of NPC via epigenetic activation of the Wnt/β-catenin pathway.
Signal Transducer and Activators of Transcription (STAT) is a set of transcription factors, involved in diverse cellular functions. Evidences from cell lines, mouse models and human tissues implicate these transcription factors in the oncogenesis of breast cancer. However, the diverse expression patterns and prognostic values of 7 STATs remain to be elucidated. In the current study, we mined the transcriptional and survival data of STATs in patients with breast carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and cBioPortal. It was found that STAT1/2 were up-regulated, whereas STAT3/4/5A/5B were down-regulated in BC patients compared with the normal tissues. The expressions of STAT5A/5B/6 were correlated with decreased levels of histological differentiation. In survival analyses through the Kaplan-Meier plotter database, high transcription levels of STAT2/4/5A/5B/6 were associated with better relapse-free survival (RFS) in all BC patients. Conversely, high STAT3 predicted shorter RFS in BC patients, suggesting that STAT3 is potential targets for precision therapy to BC patients. These data also provided STAT5A/5B/6 as new biomarker for BC prognosis.
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