DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus. Aberrantly methylated-DEGs were analyzed with R software. The Cancer Genome Atlas (TCGA) RNA sequencing and DNA methylation (Illumina HumanMethylation450) databases were utilized for validation. In total, 27 aberrantly methylated genes accompanied by altered expression were identified. After confirmation by The Cancer Genome Atlas (TCGA) database, 2 hypermethylated-low-expression genes (FAM135B and ZNF610) and 2 hypomethylated-high-expression genes (HOXA9 and DCC) were identified. A receiver operating characteristic (ROC) curve confirmed the diagnostic value of these four methylated genes for HNSCC. Multivariate Cox proportional hazards analysis showed that FAM135B methylation was a favorable independent prognostic biomarker for overall survival of HNSCC patients.

IntroductionCircular RNAs, as a class of long-time-ignored non-coding RNA, have been revealed as multifunctional RNAs in recent years, especially in the cancer research. However, the mechanism of most circular RNAs and their clinical application values in human cancers remain unknown, including in colorectal cancer (CRC).MethodsIn this study, we focused on the expression pattern and clinical values of hsa_circ_0000711 in CRC. The expression level of hsa_circ_0000711 in 101 paired CRC tissues and 3 CRC cell lines (HCT116, COLO205, and H-T29), as well as human normal colon epithelial cell line NCM460, were measured by quantitative real-time polymerase chain reaction.ResultsOur results revealed that the expression level of hsa_circ_0000711 was significantly downregulated in CRC tissues (P=9.35E-16) and CRC cell lines (P<0.01). In addition, the area under the receiver characteristic curves was 0.81. The sensitivity and specificity were 0.91 and 0.58, respectively. Meanwhile, our study showed that low expression of hsa_circ_0000711 could serve as an independent prediction biomarker associated with poor overall survival of CRC patients (hazard ratio =2.409; 95% CI: 1.276–4.547; P=0.004).ConclusionAll of these results indicated that hsa_circ_0000711 may play a crucial role in CRC carcinogenesis and could be a potential effective biomarker for the diagnosis and prognosis of CRC.

As one of crucial epigenetic modification, DNA methylation plays an important role during the carcinogenesis of colorectal cancer (CRC). In the current study, we used a human genome methylation array to detect the aberrant methylation genes in CRC. We further identified the hypermethylation of claudin-11 (CLDN11) and proved inverse correlation between CLDN11 methylation and its expression in CRC. In vitro experiments showed debased migration ability of colonic cancer cells in accompany with the converted methylation of CLDN11 after colonic cancer cells treated with demethylation agent, 5-aza-2’-deoxycytidine. Besides, our results also represented that hypermethylation of CLDN11 was associated with increased metastatic potential of CRC and with low progression free survival (PFS) of CRC. In conclusion, our findings supported that the hypermethylated CLDN11 is associated with metastasis of CRC and prognosis of poor survival of CRC.

Gene methylation has been frequently observed in lung cancer. However, the use of methylated genes in bronchial aspirates of patients with lung cancer remains to be evaluated. The purpose of this study was to analyze whether the detection of genes with aberrant promoter methylation can be useful noninvasive biomarkers in bronchial aspirates from lung cancer. We found that the methylation status of the cyclin-dependent kinase inhibitor 2A (P16), Ras association domain family 1 isoform (RASSF1A), adenomatous polyposis coli (APC) and short stature homeobox 2 (SHOX2) genes was significantly correlated with lung cancer in bronchial aspirates. The P16, RASSF1A and APC methylation had a bad diagnostic effect in bronchial aspirates of patients with lung cancer compared with non-tumor controls (P16: sensitivity = 0.26, specificity = 0.99, area under the curve (AUC) = 0.67; RASSF1A: sensitivity = 0.40, specificity = 0.99, AUC = 0.66; APC: sensitivity = 0.17, specificity = 0.98, AUC = 0.65). The pooled sensitivity, specificity, and AUC of the SHOX2 methylation were 0.75, 0.94, and 0.94, respectively. Moreover, when squamous cell carcinoma (SCC) was compared to adenocarcinoma (AC), the SHOX2 gene had a significantly higher methylation rate in SCC than in AC (P < 0.001). Methylated P16, RASSF1A, APC and retinoic acid receptor beta2 (RARβ2) genes had similar frequencies in these two histotypes (P > 0.1). Our findings suggest that methylated SHOX2 gene could be a specific and potential noninvasive biomarker using bronchial aspirates for lung cancer diagnosis, especially for SCC.

BackgroundColonic neuroendocrine neoplasms (NENs) are relatively rare tumors with an incidence rate of 0.11–0.21/100,000. NENs account for approximately 0.4% of colorectal neoplasms. Cutaneous metastases of colonic neuroendocrine carcinomas (NECs) are very infrequent, while cases of scalp metastasis are even fewer. Cutaneous metastases are more rare than visceral metastases and usually develop later; therefore, cutaneous metastases as initial distant metastases can be easily overlooked. This is the second case report of a colonic NEC with scalp metastasis. Compared with the previous case, in this instance scalp metastasis developed before visceral metastasis, and the cutaneous lesions were confined to the scalp alone.Case presentationA 62-year-old Chinese man, who had undergone radical surgery for a “locoregional” colonic NEC one and half months before, came to our hospital for adjuvant chemotherapy. We found multiple scalp nodules during physical examination. Moreover, these nodules had occurred and had not been detected prior to the patient undergoing radical surgery. The scalp nodules proved to be metastases from colonic NEC as determined using pathological and immunohistochemical examinations following lumpectomy. After one and half months, visceral metastases were detected in this patient. Ultimately, the patient died two months later.ConclusionsIn this report an unusual case of a colonic NEC with initial distant metastasis confined to the scalp is presented. This case is unusual because of the development of cutaneous metastasis before visceral metastasis. The scalp metastasis were initially overlooked, leading to inaccurate staging and radical surgery that was not curative. This demonstrates that distant metastasis can occur during the early phase of tumor growth in these aggressive lesions. Thus, the possibility of distant metastases should be assessed in the initial work up to avoid mistaken clinical staging especially when distant metastases occur only in skin.