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Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma.

ABSTRACT: The prognosis of most patients with papillary thyroid carcinoma (PTC) is excellent despite some cases of tumor progression or relapse. The present study was designed to reveal possible prognostic risk indicators for PTC. Differentially expressed genes (DEGs) extracted from 4 Gene Expression Omnibus (GEO) cohorts were subjected to functional enrichment analyses by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. A dataset from The Cancer Genome Atlas (TCGA) was obtained to filter and validate significant genes using cytoHubba, followed by analysis of their association with clinicopathological characteristics and prognosis. In total, 240 DEGs were identified after data preprocessing. These DEGs were enriched in 'intracellular redox equilibrium', 'release of exosome', 'cell adhesion', 'regulation of extracellular matrix', 'collagen binding' and 'energy metabolism' based on GO analysis which including cellular component, molecular function and biological process. KEGG pathway analysis revealed that the DEGs were enriched in thyroid hormone synthesis, pathways in cancer, focal adhesion, metabolic pathways, apoptosis, PPAR signaling pathway and PI3K/AKT signaling pathway. Using cytoHubba, the following hub genes were identified: Apolipoprotein E (APOE); hemoglobin subunit ?1 (HBA1); angiotensin II receptor 1 (AGTR1); collagen I ?1 (COL1A1); galectin 3 (LGALS3) and TIMP metallopeptidase inhibitor 1 (TIMP1). The expression of these genes was found to be consistent in TCGA datasets. Kaplan-Meier analysis revealed that APOE was significantly associated with overall survival (P=0.00067) and disease free survival (P=0.00220). Additionally, low expression of APOE was significantly associated with older age (P<0.001) and higher TNM stage (P<0.001) compared with the high expression group. Therefore, APOE may function as a predictive risk indicator for progression as well as prognosis of PTC.

SUBMITTER: Jiang Q

PROVIDER: S-EPMC7039105 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma.

Jiang Qunguang Q Feng Wenqian W Xiong Chengfeng C Lv Yunxia Y

Oncology letters 20200117 3

The prognosis of most patients with papillary thyroid carcinoma (PTC) is excellent despite some cases of tumor progression or relapse. The present study was designed to reveal possible prognostic risk indicators for PTC. Differentially expressed genes (DEGs) extracted from 4 Gene Expression Omnibus (GEO) cohorts were subjected to functional enrichment analyses by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. A dataset from The Cancer Genome Atlas (TCGA) w ...[more]

PMID: 32194729

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Project description:The aim of the present study was to evaluate the association between coexisting lymphocytic thyroiditis (LT) and the clinicopathological features of papillary thyroid carcinoma (PTC). The records of 458 patients with PTC who underwent a total thyroidectomy and lymph node dissection in Sir Run Run Shaw Hospital (Hangzhou, China) were analyzed. In accordance with the histopathology of thyroid parenchyma, the cases were divided into three groups, including Hashimoto's thyroiditis (HT), non-Hashimoto's type LT (NHLT) and no LT. Based on the histopathology, data on age, sex, maximum diameter of tumor, multifocality, extrathyroidal extension, metastatic lymph node size, extranodal extension and tumor grades in the different groups were analyzed and compared. The prevalence of coexisting LT was 29.0% (133/458), of which 7.6% (35/458) was HT and 21.4% (98/458) was NHLT. PTC concomitant with LT was significantly associated with female patients (95.5 vs. 70.2%; P<0.001), a lower rate of extrathyroidal extension and/or capsular invasion (25.6 vs. 39.7%; P=0.004), central lymph node metastasis (CLNM) ratio (10.71 vs. 17.37; P=0.014), higher number of dissected central lymph nodes (16.83 vs. 11.7; P<0.001), larger metastatic lymph nodes (0.66 vs. 0.46 cm; P<0.001), higher occurrence of multifocality (61.7 vs. 50.5%; P=0.029) and earlier pT stage (57.9 vs. 38.8%; P<0.001), regardless of the combined or separate consideration of HT and NHLT. Besides, LT was associated with multifocality [odds ratio (OR), 1.578; 95% confidence interval (CI), 1.046-2.382; P=0.030]. Furthermore, in patients with PTC, CLNM had a significant association with the male sex (OR, 2.000; 95% CI, 1.216-3.288; P=0.006), an age of <45 years (OR, 0.592; 95% CI, 0.398-0.879; P=0.009) and a tumor size of >1 cm (OR, 3.913; 95% CI, 2.431-5.734; P<0.001). In conclusion, patients with PTC and LT showed a greater female preponderance, multifocality, a lower extrathyroidal extension and a lower CLNM ratio. LT was associated with an increased risk of multifocality in PTC.

Project description:BackgroundPapillary thyroid cancer (PTC) is reported to be highly heritable in epidemiological studies. Genome-wide association studies (GWAS) have uncovered several variants associated with PTC predisposition. It remains unknown whether these variants might contribute to better clinical stratification of PTC patients.MethodsIn order to assess the usefulness of germline genetic analyses in the management of PTC patients, the genotypes of five variants (rs965513, rs944289, rs116909374, rs2439302, and rs966423) were determined in 1216 PTC patients and 1416 controls. Additionally, the expression of seven genes located close to GWAS variants (PTCSC3, MBIP, NKX2-1, FOXE1, DIRC3, PTCSC2, and NRG1) were measured in 73 PTC paired tumor/normal tissues, respectively. Next, the association was analyzed between the genotypes of the germline variants and the levels of gene expression with clinical/pathological features such as age, sex, TNM staging, multifocality status, extrathyroidal expansion, and MACIS score.ResultsThe risk allele of rs965513 was associated with larger tumor size (p = 0.025) and extrathyroidal expansion (odd ratio [OR] = 1.29, p = 0.045). The variant rs2439302 showed association with lymph node metastasis (OR = 1.24, p = 0.016), and multifocality status of the tumor (OR = 1.24, p = 0.012). The expression of MBIP was associated with T stage (p = 0.010). MBIP and PTCSC3 displayed lower expression in PTC tissue in males than in females (p = 0.025 and p = 0.036, respectively). NKX2-1 displayed lower expression in patients with N1 stage (p = 0.040).ConclusionsThe studied germline risk alleles predisposing to PTC were associated with a more aggressive course of the disease reflected by larger tumor diameter, higher multifocality rate, and more advanced N stage at the time of diagnosis. These results show that germline variants not only predispose to PTC but also might impact its clinical course. However, these associations were only moderate, and further large multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients.

Project description:ImportanceMultifocality is common in papillary thyroid carcinoma (PTC), but it is unclear whether multifocal tumors are associated with tumor recurrence or cancer-specific survival.ObjectiveTo compare tumor recurrence rates in patients with multifocal vs unifocal PTCs.Data sourcesWe searched PubMed, SCOPUS, Web of Science Core Collection, and Cochrane Database of Systematic Reviews for pertinent studies published in English from inception to June 30, 2020.Study selectionThe search strategy yielded 26 studies that compared tumor recurrence in patients with multifocal vs unifocal PTC.Data extraction and synthesisData was extracted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Characteristics of study populations and hazard ratio (HR) of multifocality were independently extracted by 2 investigators.Main outcomes and measuresThe primary outcome was tumor recurrence and the secondary outcome was cancer-specific survival. Subgroup analysis of the primary outcome was based on primary tumor size, number of tumor foci, and patient age.ResultsAmong 26 studies with a total of 33 976 patients, recurrence rates were significantly higher in patients with multifocal PTC than in those with unifocal PTC (pooled HR, 1.81; 95% CI, 1.52-2.14). Cancer-specific survival was comparable between the groups (HR, 1.19; 95% CI, 0.85-1.68). In subgroup analyses, the HRs of multifocality for recurrence were associated with primary tumor size (HRs for PTC ≤1 cm and >1 cm were 1.81 and 1.90, respectively), number of tumor foci (HRs for 2 foci and ≥3 foci were 1.45 and 1.95, respectively), and patient age (HRs for pediatric and adult patients were 3.19 and 1.89, respectively).Conclusions and relevanceThis systematic review with meta-analysis found that multifocality was significantly associated with an increased risk of recurrence in patients with PTC, while cancer-specific survival showed no difference. Differences in tumor size, number of tumor foci, and patient age should be considered when interpreting the multifocality and the risk of recurrence.

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Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma.

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Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma.

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