Yusufu Maimaiti

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.

Is papillary thyroid microcarcinoma an indolent tumor?: A retrospective study on 280 cases treated with radioiodine

AbstractThe increasing detection of papillary thyroid microcarcinoma (PTMC) has created management dilemmas. To clarify the clinical significance of postsurgery stimulated thyroglobulin (ps-Tg) in PTMC who undergo thyroidectomy and radioactive iodine (RAI), we retrospectively reviewed the 358 PTMC patients who were treated with RAI and followed up in our hospital. Those with an excessive anti-Tg antibody, ultrasound-detected residual were excluded, thereby resulting in the inclusion of 280 cases. Their clinical and histopathological information and clinical outcomes were collected and summarized. Tumor stages were classified according to the tumor, node, metastasis (TNM) staging system and the consensus of the European Thyroid Association (ETA) risk stratification system, respectively. Kaplan–Meier curves were constructed to compare the disease-free survival (DFS) rates of different risk-staging systems. By the end of follow-up, none of the patients died of the disease or relapsed. The 8-year DFS rate was 76.9%. Kaplan–Meier curves showed different DFS rates in TNM stages I versus IV, III versus IV, very low risk versus high risk, low risk versus high risk, respectively (P < 0.05), while they were not significantly different in stage I versus stage III, very low risk versus low risk (P > 0.05). Finally, 40 (14.3%) cases got a persistent disease. Five variables (male sex, nonconcurrent benign pathology, initial tumor size >5 mm, lymph node metastasis, and ps-Tg ≥ 10 &mgr;g/L) were associated with disease persistence by univariate regression analysis. Ps-Tg ≥ 10 &mgr;g/L was the only independent prognostic variable that predicted disease persistence by multivariate regression analysis (odds ratio: 36.057, P = 0.000). Therefore, PTMC with a small size of ⩽1 cm does not always act as an indolent tumor. In conclusion, ps-Tg ≥ 10 &mgr;g/L is associated with increased odds of disease persistence. ETA risk stratification is more effective in predicting disease persistence than the TNM classification system.

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.

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity.

Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis

Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L) expression is detected in various types of tumors; insulin induces the phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner. However, little is known about the expression and role of SSH-1L in breast cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L expression by immunohistochemistry. The correlation between SSH-1L level and patients’ clinical characteristics was analyzed with Pearson’s χ2 test. The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in 88.1% of tissue specimens by immunohistochemistry and was strongly associated with increased metastasis and mortality. Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment.

Combination of SIRT1 and Src overexpression suggests poor prognosis in luminal breast cancer

Objectives 1) Analyze the correlation of SIRT1 and Src with human breast cancer (BC) prognosis; 2) explore the roles of SIRT1 and Src in BC cell proliferation, tumor invasion, and metastasis; and 3) analyze the correlation and interaction between SIRT1 and Src. Materials and methods 1) Tissue microarray was used to analyze the expression of SIRT1 and Src in human BC tissues and the correlation between protein expression and cancer prognosis; 2) CCK8 assay was used to determine the influence of SIRT1 and Src inhibitors on BC cell proliferation; 3) Transwell migration assay and wound healing assay were used to determine the effect of SIRT1 and Src inhibitors on BC cell migration and invasion; and 4) Western blotting was used to analyze the correlation and interaction between SIRT1 and Src. Results 1) Combination of SIRT1 and/or Src positivity is a prognosis factor in BC, especially in luminal type; 2) MCF-7 cell proliferation is suppressed by SIRT1 inhibitor Ex527, and cell migration and invasion were inhibited by Src inhibitor bosutinib; 3) combined with Ex527, bosutinib has a significantly increased effect on MCF-7 cell migration suppression; and 4) there is a positive association between SIRT1 and Src both in BC tissues and in MCF-7 cells. Conclusion 1) SIRT1 and Src overexpression are both correlated with poor prognosis in human BC; 2) SIRT1 + Src (SIRT1 and/or Src positivity) is a fine prognosis model for luminal-type BC; 3) SIRT1 is a copromotor of Src in BC migration and invasion, but not in cell proliferation; and 4) our results suggest a potential interaction or a common regulation pathway between SIRT1 and Src expression and activity.

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.

SSH1 expression is associated with gastric cancer progression and predicts a poor prognosis

BackgroundSlingshot homolog-1 (SSH1) plays an important role in pathological processes, including in the occurrence and development of tumours. The purpose of this study was to determine whether SSH1 is a key biomarker with prognostic value for survival in patients with gastric cancer.MethodsWe performed immunohistochemistry (IHC) on tissue microarrays containing 100 gastric cancer specimens to evaluate SSH1 protein expression. The association of pathological characteristics with cumulative survival was determined by Kaplan-Meier analysis. A Cox proportional hazards model was generated in the multi-factorial survival analysis to identify univariate prognostic factors of GC.ResultsSSH1 expression level in gastric cancer tissues was significantly associated with lymph node metastasis (P = 0.032). Additionally, multivariate regression analysis clearly indicated that SSH1 expression was significantly correlated with poor clinical outcomes of patients with gastric cancer (P = 0.016). Multivariate analyses showed that SSH1 was the best predictor of poor prognosis in patients with gastric cancer (P = 0.030).ConclusionsSSH1 expression is associated with gastric cancer progression and predicts a poor prognosis. SSH1 may play an important role in the development of gastric cancer, and it is a promising target for prevention and/or treatment of gastric cancer.

Overexpression of cofilin correlates with poor survival in breast cancer: A tissue microarray analysis

Cofilin, a key regulator of actin cytoskeleton dynamics, is considered to be involved in cellular migration, tumor invasion and mitosis, and its activity is increased in cancer cells. To address the association between cofilin and breast cancer prognosis, which is unclear at present, cofilin expression was analyzed in tissue microarrays of tumors from 310 patients with breast cancer via immunohistochemistry. In a multivariate Cox regression analysis, a high expression of cofilin in tumor cells correlated significantly with shorter overall survival (hazard ratio, 2.22; 95% confidence interval, 1.35–3.66, P=0.002, and with the Nottingham histologic grade, Ki-67 status and human epidermal growth factor receptor 2 status (P=0.031, 0.001, and 0.001, respectively). Cofilin expression was not observed as correlated with estrogen or progesterone receptor expression, tumor size or lymph node status. These data demonstrate that cofilin is associated with poor outcome, thereby suggesting that it is a potential prognostic factor in breast cancer.