Zeming Liu

Prognostic and Clinicopathological Value of Programmed Death Ligand-1 in Breast Cancer: A Meta-Analysis

Recently, the interest in programmed death ligand-1 (PD-L1) as a prognostic marker in several types of malignant tumors has increased. In the present meta-analysis, we aimed to explore the prognostic and clinicopathological value of PD-L1 in breast cancer. We searched Medline/PubMed, Web of Science, EMBASE, the Cochrane Library databases, and grey literature from inception until January 20, 2016. Studies concerning breast cancer that focused on PD-L1 expression and studies reporting survival data were included; two authors independently performed the data extraction. The pooled risk ratio (RR) and 95% confidence interval (CI) were assessed to determine the association between the clinicopathological parameters of patients and PD-L1 expression. Five studies involving 2061 patients were included in this meta-analysis. The results indicated that positive/higher PD-L1 expression was a negative predictor for breast cancer, with an RR of 1.64 (95% CI, 1.14–2.34) for the total mortality risk and an RR of 2.53 (95% CI, 1.78–3.59) for the mortality risk 10 years after surgery. Moreover, positive/higher PD-L1 expression was significantly associated with positive lymph node metastasis (RR, 1.33; 95% CI, 1.04–1.70), poor nuclear grade (RR, 1.24; 95% CI, 1.07–1.43), and negative estrogen receptor status (RR, 2.45; 95% CI, 1.31–4.60) in breast cancer patients. Our findings suggest that PD-L1 can serve as a significant biomarker for poor prognosis and the adverse clinicopathologic features of breast cancer and could facilitate the better management of individual patients.

TERT promoter Mutation and Its Association with Clinicopathological Features and Prognosis of Papillary Thyroid Cancer: A Meta-analysis.

We performed a meta-analysis to elucidate the associations of the clinicopathological characteristics and prognostic factors of papillary thyroid cancer (PTC) with TERT promoter mutations. A literature search was performed of the PubMed and EMBASE databases using Medical Subject Headings and keywords. Individual study-specific odds ratios (ORs) and confidence intervals (CIs) were calculated. The average prevalence rate of TERT promoter mutations was 10.1%. TERT promoter mutations occurred more frequently in patients with larger tumors (p = 0.003). TERT promoter mutations were associated with advanced stage (OR = 3.11, 95% CI = 2.22–4.36), lymph node metastasis (OR = 1.82, 95% CI = 1.12–2.96), distant metastasis (OR = 4.18, 95% CI = 1.61–10.81), BRAF mutation positivity (OR = 2.71, 95% CI = 1.45–3.24), recurrence (OR = 3.91, 95% CI = 1.83–8.34), and mortality (OR = 8.13, 95% CI = 3.77–17.53). The associations of TERT promoter mutations with extrathyroidal invasion (OR = 1.98, 95% CI = 0.96–4.07), unifocality (OR = 1.36, 95% CI = 0.90–2.07), and vascular invasion (OR = 1.45, 95% CI = 0.92–2.30) were not significant. TERT promoter mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in PTC.

A comparison of the clinicopathological features and prognoses of the classical and the tall cell variant of papillary thyroid cancer: a meta-analysis

Papillary thyroid cancer (PTC) accounts for 80–90% of all thyroid malignancies. The tall cell variant (TCV) is a rare aggressive histotype of PTC. We performed a meta-analysis to compare the clinicopathological characteristics and prognostic factors of TCV with those of classical papillary thyroid carcinoma (cPTC). A literature search was performed using the PubMed and EMBASE databases using Medical Subject Headings and keywords. Twenty studies that included 1871 patients with TCV and 75323 patients with cPTC were included in our meta-analysis. Odds ratios and confidence intervals were calculated for each study. Patients with TCV were associated with multifocality, higher TNM stage, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, BRAF mutation, disease-specific survival, and overall survival. We found that TCV cases were associated with more aggressive clinicopathological characteristics and poorer prognoses than cPTC cases were. Our results suggest that TCV is a high-risk PTC that warrants aggressive treatment and follow-up strategies.

Dephosphorylated cofilin expression is associated with poor prognosis in cases of human breast cancer: a tissue microarray analysis

Background Proteins in the cofilin pathway regulate actin dynamics and may be involved in cancer cell migration and invasion. However, there are no direct data that suggest that dephosphorylated cofilin can affect breast cancer prognosis. Methods We assessed the expressions of cofilin and phosphorylated cofilin (P-cofilin) in breast cancer tissue microarrays (290 patients, mean follow-up: 95.7±2.49 months) to evaluate dephosphorylated cofilin and its relationship with breast cancer prognosis. The associations of pathological characteristics with cumulative survival were evaluated using Kaplan–Meier analysis. Results Univariate analyses revealed that overall survival was associated with cofilin levels, N category, TNM stage, estrogen receptor status, progesterone receptor status, and molecular subtypes. Cofilin status and TNM stage independently affected overall survival, although P-cofilin expression was not associated with patient survival. In the P-cofilin-negative subgroup, cofilin expression was significantly associated with patient survival, although cofilin expression was not significantly associated with patient survival in the P-cofilin-positive subgroup. We further analyzed the P-cofilin-negative cases and found that Ki-67 expression was significantly elevated in the subgroup that was strongly positive for cofilin (P=0.002). Conclusion Among P-cofilin-negative patients with breast cancer, cofilin expression defines a population of patients with lower overall survival, which suggests that dephosphorylated cofilin expression might predict the prognosis in cases of P-cofilin-negative breast cancer. Furthermore, our results suggest that inhibitors of dephosphorylated cofilin expression may provide therapeutic benefits in patients with breast cancer.

Diagnostic accuracy of ultrasonographic features for lymph node metastasis in papillary thyroid microcarcinoma: a single-center retrospective study

BackgroundWhether sonography is an appropriate imaging modality for cervical lymph nodes in patients with papillary thyroid microcarcinoma (PTMC) remains unclear. Hence, this study aimed to evaluate the diagnostic value of ultrasonography (US) features for lymph node metastasis in PTMC.MethodsSeven hundred twelve patients with PTMC who underwent conventional ultrasonography examinations of the cervical lymph nodes were included. All included cases underwent total thyroidectomy plus prophylactic central lymph node dissection. The included lymph nodes were marked superficially, and the corresponding lymph nodes were completely removed and sent for pathological examination. The US features of lymph nodes with and without metastasis were compared, and the odds ratios of the suspicious US features were determined with univariate and multivariate analyses.ResultsRound shape, loss of an echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were significantly more common in metastatic than nonmetastatic lymph nodes, whereas the boundary and echo did not significantly differ. Multivariate logistic regression analysis showed that round shape, loss of echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were independent predictive factors for the assessment of metastatic lymph nodes. Round shape had the highest sensitivity of all variables, while loss of an echogenic fatty hilum had the highest specificity and accuracy. The area under the receiver operating characteristic curve, which was calculated to verify the relationship between the various US features and metastatic lymph nodes, was 0.793.ConclusionsOur study found that the US features of round shape, cystic change, calcification, loss of echogenic fatty hilum, and abnormal vascularity were useful sonographic criteria for differentiating between cervical lymph nodes with and without metastasis.

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF‐7 in cooperation with DNMT1. This was similar to the effect of 5‐Aza‐CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF‐7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer.

Total tumour diameter is superior to unifocal diameter as a predictor of papillary thyroid microcarcinoma prognosis

The current American Joint Committee (AJCC) on Cancer TNM classification does not describe the treatment of multifocal papillary thyroid microcarcinomas (PTMCs) with a total tumour diameter (TTD) >1 cm. Herein, we investigated this PTMC subgroup in terms of extrathyroidal extension (ETE), local infiltration, central lymph node metastasis (LNM), and prognosis. Consecutive patients (n = 1102) were identified and the proportions of LNM, ETE, and local infiltration were similar between PTCs with a unifocal tumour diameter >1 cm and ≤2 cm and PTMCs with a multifocal TTD >1 cm and ≤2 cm. The proportions of LNM, ETE, and local infiltration were also similar between PTMCs with a unifocal diameter ≤1 cm vs. multifocal TTD ≤1 cm. However, when comparing PTMCs with a unifocal diameter ≤1 cm vs. multifocal TTD >1 cm, significant differences were observed. In the Kaplan-Meier analysis, significant differences were observed between PTMCs with a unifocal diameter ≤1 cm vs. multifocal TTD >1 cm and multifocal TTD ≤1 cm vs. multifocal TTD >1 cm. Accordingly, TTD may represent a more accurate criterion for tumour size of PTCs and should be considered in the revised AJCC staging system.

Prognostic and clinicopathological value of GATA binding protein 3 in breast cancer: A systematic review and meta-analysis

The potential prognostic value of GATA binding protein 3 (GATA3) in breast cancer has recently increased, although the evidence is inconclusive. This meta-analysis of 10 articles involving 5,080 breast cancer patients explored the prognostic and clinicopathological value of GATA3 in breast cancer. Time to tumor progression (TTP) and overall survival (OS) were primary endpoints. Pooled hazard ratio (HR), pooled risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate the association between GATA3, prognosis, and clinicopathological parameters. High GATA3 expression predicts breast cancer, with a HR (HR = 0.671; 95% CI = 0.475–0.947; P = 0.023) of TTP, but is not associated with OS (HR = 0.889; 95% CI = 0.789–1.001; P = 0.052). GATA3 overexpression is associated with positive ER (RR = 3.155; 95% CI = 1.680–5.923; P = 0.000), positive PR (RR = 3.949; 95% CI = 1.567–9.954, P = 0.004), lower nuclear grade (RR = 0.435; 95% CI = 0.369–0.514; P = 0.000), and smaller tumor size (RR = 0.816; 95% CI = 0.709–0.940; P = 0.005). High GATA3 expression may predict TTP in breast cancer, and such patients may show better clinicopathological features.

Correction: Mixed subtype thyroid cancer: A surveillance, epidemiology, and end results database analysis

[This corrects the article DOI: 10.18632/oncotarget.21242.].

CPT1A regulates breast cancer-associated lymphangiogenesis via VEGF signaling

BACKGROUND Lymphangiogenesis is critical for metastasis of a variety of cancers, including breast cancer. CPT1A (carnitine palmitoyltransferase 1a) has been reported to play a critical role in breast cancer progress. However, the molecular mechanism remains elusive. METHODS In order to investigate the role of CPT1A in HDLEC cells, short hairpin RNA approach was utilized to knock down the CPT1A gene expression. We employed transwell and lymphatic vessel formation assay to examine invasion and lymphangiogenesis of HDLEC (Human dermal lymphatic endothelial cells). RT-qPCR and westernblot analyses were used to determine genes expression in HDLEC and breast cancer cells. Finally, we determined the relative rate of acetyl-CoA/CoA in shNC and shCPT1A HDLEC cells by LC-MS approach. RESULTS Knockdown of CPT1A in breast cancer cells (MCF-7 and MDA-MB-231) abolished invasion and lymphangiogenesis of HDLEC cells. Mechanistically, CPT1A depletion suppressed the expression of VEGF-C and VEGF-D in MCF-7 and MDA-MB-231 cells. Interestingly, CPT1A knockdown in HDLEC cells exhibited attenuated expression of lymphangiogenic markers (podoplanin, VEGFR-3, VEGF-C, VEGF-D and PROX-1). Consistently, CPT1A -null HDLEC cells displayed compromised invasion and lymphangiogenesis compared with negative control. Further investigation revealed that CPT1A regulated VEGFR3 via acetyl-CoA mediated H3K9ac, which could be abrogated by supplement of acetate. CONCLUSIONS In present study, we revealed the mechanism by which CPT1A regulates breast cancer-associated invasion and lymphangiogenesis. Our findings provide insights into CPT1A -promoted breast tumor metastasis and provide rationale for understanding breast cancer metastasis.