Background and Aim
Single‐nucleotide polymorphisms (SNPs) in long non‐coding RNAs (lncRNAs) are potential biomarkers for cancer risk, but their association with hepatocellular carcinoma (HCC) is ...unclear. We examined the association of lncRNA‐related SNPs with HCC susceptibility and explored the optimal genetic models for SNPs.
Methods
Five candidate SNPs linked with digestive tumors were first genotyped in a screening population of 700 HCC and 2800 control cases. The association between each SNP and HCC risk was estimated by multivariate logistic regression adjusted by sex and age and recorded as odds ratio (OR) with 95% confidence interval. Significant associations were further tested in a validation population with 1140 HCC and 5115 control cases. Finally, the most appropriate genetic models for HCC‐associated SNPs were identified using pairwise allele differences; the overall gene effects of each SNP were further evaluated based on optimal genetic models.
Results
Three candidate SNPs, rs7315438, rs6983267, and rs10795668, showed statistical connections with HCC risk in the discovery stage. Among these, rs7315438 remained steadily significant in the validation stage; rs7315438 and rs10795668 both reached statistical threshold in the combined analysis of both stages. SNP rs7315438 (TC vs TT/CC, OR = 1.410, P < 0.001) was associated with increased risk of HCC in a complete overdominant model, whereas rs10795668 (AG vs AA/GG, OR = 0.892, P = 0.035) exerted a protective effect on HCC risk in a complete overdominant model.
Conclusions
Long non‐coding RNA‐related SNPs rs7315438 and rs10795668 are potential biomarkers for HCC susceptibility, especially when evaluated based on their optimal genetic models.
Objectives
Ultrasound (US)-guided fine needle aspiration cytology (FNAC) and thyroglobulin measurement (FNA-Tg) are two common methods for confirming lymph node metastases (LNM) in patients with ...differentiated thyroid carcinoma (DTC). This study aimed at comparing the diagnostic performance of FNAC, FNA-Tg alone, and in combination by means of a meta-analysis.
Methods
Eligible articles were selected according to predefined criteria, and their quality was evaluated as per the QUADAS-2 checklist. We calculated pooled sensitivity (Se), specificity (Sp), positive/negative likelihood ratio, and diagnostic odds ratio (DOR), and plotted the summary receiver operating characteristic (SROC) curve using the Meta-DiSc1.4 software.
Results
Twenty-one studies pooling 1662 malignant and 1279 benign LNs from 2712 patients with DTC were included. The results showed that FNAC was more specific (pooled Sp, 0.98) while FNA-Tg was more sensitive (pooled Se, 0.94). FNAC and FNAC+FNA-Tg performed better postoperatively than FNA-Tg, while FNA-Tg performed better preoperatively. The combination of FNAC and FNA-Tg could achieve a better diagnostic performance than each alone (DOR 446.00, area under the curve AUC 0.9862), no matter preoperatively (DOR 378.14, AUC 0.9879) or postoperatively (DOR 788.72, AUC 0.9930). Besides, the combination of FNAC and FNA-Tg/serum-Tg ratio obtained a higher Sp (0.98) than the combination of FNAC and FNA-Tg.
Conclusion
The addition of FNA-Tg, especially the FNA-Tg/serum-Tg ratio, to FNAC could increase the diagnostic performance of LNM in both preoperative and postoperative patients with DTC. Since one test or test combinations could perform differently according to the clinical situation, the best-fitting test should be chosen accordingly.
Key Points
•
FNAC is more specific than FNA-Tg while FNA-Tg is more sensitive than FNAC
.
•
The combination of FNAC and FNA-Tg could achieve a better diagnostic performance than either alone, no matter preoperatively or postoperatively
.
•
The combination of FNAC and FNA-Tg/serum-Tg ratio could reach a higher Sp than the combination of FNAC and FNA-Tg
.
Background
Gene mutations may play an important role in the development, response to treatment and prognosis of colorectal cancer (CRC). This retrospective study aimed to investigate the mutation ...profiling of Chinese patients with CRC, and its correlation with clinicopathological features and prognosis.
Methods
This study included 1190 Chinese CRC patients who were diagnosed between May 1998 and December 2018 and received clinical genetic testing. The OncoCarta Panel was used to test a total of 238 possible mutations in 19 common oncogenes.
Results
Five hundred and eighty‐two (48.9%) cases were detected with gene mutations. Of the 582 cases, there were 111 cases (19.7%) with two concurrent mutations, and six cases (1.0%) with three concurrent mutations. KRAS was the most common gene mutation that occurred in all cases (429, 36.1%), followed by PIK3CA (121, 10.2%), NRAS (47, 3.9%), BRAF (35, 2.9%), HRAS (11, 0.9%) and epidermal growth factor receptor (EGFR) (11, 0.9%). AKT1, KIT, FGFR1, FGFR3, FLT3, CDK, ERBB2, ABL1, MET, RET and PDGFRA mutations were also detected in several cases. When it came to prognosis, we found that KRAS/NRAS/PIK3CA/BRAF mutation was not associated with prognosis. But BRAF mutation was associated with poor prognosis in patients who accepted anti‐EGFR therapy.
Conclusions
The molecular testing offered the clinical data and mutation profile of Chinese CRC patients. The information of these mutated genes may help to find out the correlation between mutated genes and the development or prognosis of CRC.
This is the largest sample size from Chinese colorectal cancer patients about gene mutation profiling. We found that KRAS was the most common mutated gene, followed by PIK3CA, NRAS and BRAF genes. BRAF mutation was associated with poor prognosis in patients who accepted anti‐epidermal growth factor receptor therapy.
Long non-coding RNAs (lncRNAs) act as important biological regulators in human cancers. The purpose of this study was to identify promising biomarkers for improved diagnosis and prognosis of ...papillary thyroid cancer (PTC). We analyzed the lncRNA expression profile of PTC patients and identified five upregulated and three downregulated lncRNAs as diagnostic biomarkers for PTC in our cohorts, which were confirmed using The Cancer Genome Atlas (TCGA) data. Several lncRNAs have been linked with lymph node (LN) metastasis in patients with PTC. A nomogram combining two lncRNAs, lnc-MPEG1-1:1 and lnc-ABCA12-5:2, with age, T stage, histological type, and predicted LN metastasis was developed. The area under the curve of the developed nomogram was 0.77 (0.73–0.81) in the TCGA training cohort and 0.88 (0.79–0.96) in our validation cohort. In particular, in vivo and in vitro experiments showed that overexpression of lnc-MPEG1-1:1 in PTC cell lines promoted the proliferation and migration of PTC. lnc-MPEG1-1:1 is overexpressed in the cytoplasm of PTC cells and functionally promotes cellular proliferation and migration and functions as a competitive endogenous RNA (ceRNA) by competitively occupying the shared binding sequences of miR-766-5p. lnc-MPEG1-1:1 knockdown suppressed epithelial-mesenchymal transition by miR-766-5p in PTC cells. Collectively, these results revealed a lnc-MPEG1-1:1/miR-766-5p pathway for thyroid cancer progression and suggest that a nomogram effectively predicted the LN metastasis in PTC.
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A nomogram combining lnc-MPEG1-1:1 and lnc-ABCA12-5:2 with age, T stage, and histological type predicted well the metastasis of the lymph node metastasis of PTC. Moreover, lnc-MPEG1-1:1 was highlighted to promote the proliferation and migration of PTC by occupying miR-766-5p.
•PTCH common variants associated with a decreased risk of reproductive cancer.•Breast and prostate cancers shared genetic basis in PTCH1 and PTCH2.•Deleterious variants of PTCH2 might predispose a ...carrier to reproductive cancers.
PTCH1 and PTCH2 are associated with nevoid basal cell carcinoma syndrome and basal cell carcinoma. We determined the prevalence of their common and rare variants in 877 patients with various reproductive cancers and 296 healthy subjects. Using targeted next-generation sequencing, we found significantly statistical associations of the minor alleles at seven common variants of PTCH1 and PTCH2 with a decreased risk of reproductive cancers (P = 9.69 × 10−12). Among these variants, two haplotype blocks in high linkage disequilibrium were consisted of rs2277184, rs2066829 and rs2236405 sites at PTCH1 and rs3795720, rs11573590 and rs11211040 sites at PTCH2. Single marker and haplotype-based analysis consistently revealed a decreased risk of reproductive cancers especially breast and prostate cancers in the subjects carrying the minor alleles, and on the contrary, an increased risk for major alleles. Healthy control subjects showed a higher rate of rare variants than that of cancer patients (P = 0.017). Notably, two frameshift variants (p.Ser391* and p.Cys101Alafs*48) of PTCH2 with deleterious effects were found in only four cancer patients. Higher frequencies of variants of PTCH genes might have a protective role against the development of reproductive cancers, whereas rare deleterious variants of PTCH2 might predispose a carrier to reproductive cancers.
Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound has received increasing attention from ...neonatal physicians. Nevertheless, clear reference standards and guideline limits are needed for accurate application of this diagnostic modality. This document aims to summarize expert opinions and to provide precise guidance to help facilitate the use of the lung ultrasound in the diagnosis of neonatal lung diseases.
There is a compelling need to identify novel genetic variants for papillary thyroid cancer (PTC) susceptibility. The Cancer Genome Atlas (TCGA) data showed associations between SPP1 and SPARC mRNA ...overexpression and aggressive behaviors of PTC, which prompted us to assess potential associations between genetic variants in these genes and PTC risk. Three highly linked SPARC loci (rs1054204, rs3210714, and rs3549) contributed to reduced PTC risk under a codominant model (odds ratio OR, 0.79–0.80). Variant CAG alleles at these loci significantly enhanced SPARC transcription activation upon cotransfection with miR-29b and miR-495 when compared to the common alleles GGC (all P < 0.05). The three SPARC polymorphisms interacted with SPP1 rs4754, with elevated joint ORs of 2.43, 2.52, and 2.52, respectively. Additionally, interaction between SPP1 rs2358744 and SPARC rs2304052 was observed. Our study revealed associations between SPP1 and SPARC polymorphisms that, individually or in combination, are involved in PTC susceptibility.
•SPP1 and SPARC expression correlate with papillary thyroid cancer (PTC) stages.•SPARC variants at rs1054204, rs3210714 and rs3549 are related to PTC risk.•SPP1 genotype TT at rs4754 is associated with increased PTC risk.•CAG alleles in the SPARC 3′ UTR reduce the binding affinity of miR-29b and miR-495.•SPP1 rs2358744 and SPARC rs2304052 have an epistatic interaction effect.
Few reports from China provide confirmed evidence of the effectiveness of the larynx preservation strategy compared with surgery on the treatment of laryngeal and hypopharyngeal cancers. This study ...assessed the clinical outcomes of patients with locally advanced laryngeal and hypopharyngeal cancers treated with larynx preservation and determined the optimal larynx preservation procedure.
Data of 1,494 patients treated with total laryngectomy or larynx preservation between 2006 and 2014 were retrieved from the database of Sun-Yat Sen University Cancer Center in Guangzhou, China, and 366 eligible patients were selected for final analysis. The clinical outcomes of 228 patients received total laryngectomy and 138 patients received larynx preservation treatments, which comprises induction followed by radiotherapy and concurrent radio-chemotherapy, were compared.
There was no statistical difference in the 3-, 5-, and 10-year PFS and OS in patients received larynx preservation compared with patients treated with laryngectomy. With respect to T stage, a better overall OS in T2-stage disease (P = 0.036) but poorer PFS (P = 0.005) in T3-stage disease was observed in the larynx preservation group compared with the surgery group in Univariate analysis. T3-stage disease had poorer PFS in multivariable analysis (P = 0.022). With larynx preservation intent, induction chemotherapy followed by radiotherapy showed no advantage in the control of disease progression and survival compared with concurrent chemoradiotherapy. The patient subpopulations who received efficacy assessment after induction chemotherapy exhibited significantly longer PFS and OS compared with those without efficacy assessment.
This is the largest sample size study on larynx preservation treatment for laryngeal and hypopharyngeal cancers in China. Our results indicated that larynx preservation treatments did not jeopardize the survival of patients with advanced resectable laryngeal or hypopharyngeal cancers. Efficacy assessment should be emphasized in induction chemotherapy.
Objective. To investigate methylation of the adenomatosis polyposis coli homologue (APC2) promoter and its correlation with prognostic implications in Chinese colorectal cancer (CRC). Methods. The ...mRNA expression of APC2 in colorectal tissues was evaluated using the database of The Cancer Genome Atlas (TCGA). Methylation analysis of APC2 in tumor (n=66) and corresponding adjacent formalin-fixed and paraffin-embedded (FFPE) tissues (n=44) was performed by Sequenom EpiTYPER® and verified by cloning-based bisulfite sequencing analysis. Demethylation and retrieval of APC2 expression in cell lines HT29, HCT116, and SW480 were treated with 5-aza-2′-deoxycytidine (5-AZC). Results. Analysis of TCGA showed that APC2 mRNA was significantly downregulated in primary tumors when compared to normal tissues (p<0.05). APC2 methylation was upregulated (43.93% vs 7.31%, p<0.05) in tumors compared to adjacent FFPE tissues. In vitro experiments demonstrated that 5-AZC downregulated the methylation of APC2 and retrieved its expression of mRNA and protein levels (p<0.05). Multivariate Cox regression indicated that APC2_CPG_14 was an independent risk factor for overall survival (HR = 6.38, 95% CI: 1.59–25.64, p<0.05). Conclusion. This study indicates that APC2 is hypermethylated and may be a tumorigenesis biomarker for Chinese CRC patients.
To systematically investigate the prognostic implications of tripartite motif containing 24 (
) expression levels in Patients with solid tumors.
Pubmed, Embase, China National Knowledge ...Infrastructure, and Wanfang databases were searched through December 2017 to identify studies examining the relationship between
expression levels and outcomes in solid tumor patients. The hazard ratios (HRs) with corresponding 95% confidence intervals were used to evaluate the association between
and overall survival (OS).
Ten studies with 1370 patients were included. The overall pooled prevalence for
overexpression was 59.0% (
< 0.01). Moreover, the pooled HR of
for OS was 0.43 (
= 0.04) by univariate analysis in 10 articles (1370) and 0.62 (
= 0.08) by multivariate analysis in 5 studies (845).
over-expression was associated with tumor invasiveness (odds ratio OR = 2.05,
< 0.01) and tumor-node-metastasis stage (OR = 2.42,
= 0.03).
This study demonstrated that
expression levels may be a useful prognostic biomarker in patients with solid tumors.
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