Dachuan Zhang

Correlation between serum IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients

Background IL-1β is an essential factor of inflammation initiation, and it also promotes malignant transformation, indicating its tumorigenic property. We aimed to investigate the correlation between IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients. Results The IL-1β level in both LUAD and LUSC patients was significantly higher than that of healthy donors (P < 0.001). In both populations, patients with low IL-1β level had better prognosis than high IL-1β level (P < 0.001 and P = 0.010, respectively). In A549 cells, miR-144 showed the biggest expression change (−4.38 fold) after IL-1β exposure. In LUAD patients, a negative correlation was detected between IL-1β and miR-144-3p (r = –0.540, P < 0.001) and the high miR-144-3p group had better prognosis (P = 0.003), which was validated by TCGA data. Clinical stage, IL-1β and miR-144-3p were independent risk factors in LUAD patients. In vitro, IL-1β and miR-144-3p antagomir could enhance proliferation and miR-144-3p mimics would attenuate the promoting effect of IL-1β. Materials and Methods ELISA and qRT-PCR were applied respectively to detected cytokines and miR-144-3p in 129 LUAD, 54 LUSC and 40 healthy donors. Moreover, miRNA array was carried out for miRNA profiling. TCGA database was employed for validation, and follow up data were collected for prognosis evaluation. MTT assay and western-blot were carried out for proliferation evaluation. Conclusions In LUAD patients, the serum IL-1β level was correlated with miR-144-3p may affect miR-144-3p at transcriptional level. Both of them were independent risk factors for LUAD prognosis. In addition, IL-1β and miR-144-3p might mediate inflammation-promoted tumorigenesis in LUAD patients.

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis.

Background In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. Materials and methods We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity. Results A total of 31 observational studies including 4,185 patients were enrolled. For TILs subsets, the amount of CD8+, FOXP3+, CD3+, CD57+, CD20+, CD45RO+, Granzyme B+ and T-bet+ lymphocytes was significantly associated with improved survival (P < 0.05); moreover, the amount of CD3+ TILs in intra-tumoral compartment (IT) was the most significant prognostic marker (pooled HR = 0.52; 95% CI = 0.43–0.63; P < 0.001). However, CD4+ TILs was not statistically associated with patients’ survival. FOXP3+ TILs showed bidirectional prognostic roles which had positive effect in IT (pooled HR = 1.57; 95% CI = 1.04–2.37; P = 0.033) and negative effect in extra-tumoral compartment (ET) (pooled HR = 0.76; 95% CI = 0.60–0.96; P = 0.022). Conclusions This meta-analysis suggests that some TIL subsets could serve as prognostic biomarkers in gastric cancer. High-quality randomized controlled trials are needed to decide if these TILs could serve as targets for immunotherapy in gastric cancer.

Lower Bmi-1 Expression May Predict Longer Survival of Colon Cancer Patients

Background: This study aimed to investigate the Bmi-1 expression and the clinical significance in colon cancer (CC). Patients and Methods: Bmi-1 expression in tumor tissue and the corresponding normal tissue was detected using immunohistological staining. The correlations between Bmi-1 expression and clinicopathological characteristics and the overall survival (OS) time were analyzed. Results: The median H-scores of Bmi-1 in CC tissues and the corresponding tissues were 80.0 (0-270) and 5.0 (0-90), with no statistically significant difference (Z=-13.7, P<0.001). Bmi-1 expression in CC tissues was not statistically correlated with any characteristics. The median OS times for CC patients with high or low Bmi-1 expression were 53.7 months and 44.9 months, respectively, with no statistically significant difference (P = 0.123). The survival rates of patients with low Bmi-1 expression were higher than those of patients with high Bmi-1 expression but the differences were not statistically significant. Conclusion: Bmi-1 expression in CC tissue is significantly higher than that in corresponding normal tissue. While there may be a trend towards improved survival, this is not statistically significant.

Merkel cell carcinoma in the left groin: A case report and review of the literature

Merkel cell carcinoma (MCC) is a relatively rare but aggressive primary neuroendocrine carcinoma of the skin. MCC frequently occurs on sun-exposed areas in elderly Caucasian patients and has a propensity for local recurrence, regional lymph node invasion and distant metastases. However, MCC occurring on sites that are not sun-exposed in Asian patients is extremely uncommon. The current study describes the case of a 66-year-old Chinese male who presented with an asymptomatic, smooth lesion in the left inguinal region, which was initially diagnosed as a malignant lymphoma. Upon histological and immunohistochemical analysis, the tumor was consistent with the diagnosis of an MCC. In conclusion, due to its low incidence rate and lack of characteristic clinical manifestations, the final diagnosis of MCC relies on the analysis of histological findings and immunohistochemical markers following lesion biopsy or resection. The present study aimed to report a case of MCC and present a brief literature review in order to bring attention to the diagnosis of this condition.

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8+ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3+ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57+ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3+, CD4+ and CD45RO+ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

Hierarchical investigating the predictive value of p53, COX2, EGFR, nm23 in the post-operative patients with colorectal carcinoma

The aim of this study was to evaluate the correlations between p53, COX2, EGFR, nm23 expression and the progression free survival (PFS) of post-operative patients with colorectal carcinoma. Immunohistochemistry was used to detect the expression of p53, COX2, EGFR and nm23 in 459 specimens from colorectal carcinoma patients. Kaplan-Meier estimates, Cox proportional hazard regression analyses and hierarchical analyses were performed on the collected data. Kaplan-Meier estimates analysis suggested that EGFR expression was as a negative predictor, the median PFS of patients with EGFR high expression was 21.73 months, and the median PFS of patients with low EGFR expression was 57.83 months (χ2=20.880, P<0.001); nm23 expression was positive predictive factor for the prognosis of patients with colorectal carcinoma, the median PFS of patients with high nm23 expression was 37.77 months, and the median PFS was 21.47 months in the patients with low nm23 expression (χ2=7.364, P=0.007). Cox regression analysis revealed that comparing with the patients with low expression of EGFR, the patients with high EGFR expression were at higher risk of tumor progression (HR=1.667, P=0.004); Comparing with the patients with high nm23 expression, the patients with nm23 low expression had a higher risk of tumor progression (HR=0.412, P<0.001); and the risk of tumor progression was higher in the patients with high EGFR expression and low nm23 expression (HR=0.245, P<0.001). Hierarchical analysis showed that EGFR expression mainly correlates with the PFS of TNM stage I-II colorectal cancer patients, the median PFS was 33.53 months in the TNM stage I-II colorectal cancer patients with high EGFR expression patients; The median PFS of the TNM stage I-II colorectal cancer patients with low EGFR expression was 70.43 months (χ2=9.530, P=0.002); The median PFS was 19.2 months in the TNM stage III-IV colorectal cancer patients with high expression EGFR, the PFS of the TNM stage III-IV colorectal cancer patients with low EGFR expression was 37.87 months (χ2=7.97, P=0.005). nm23 expression mainly correlates with the PFS of TNM stage III-IV colorecatal cancer patients. The median PFS was 47.27 months in TNM stage I-II colorectal cancer patients with nm23 high expression, the median PFS was 48.85 months in TNM stage I-II colorectal cancer patients with low nm23 expression (χ2=0.101, P=0.750); The median PFS was 28.8 months in TNM stage III-IV colorectal cancer patients with nm23 high expression, the median PFS was 14.7 months in TNM stage III-IV colorectal cancer patients with low nm23 expression (χ2=13.213, P<0.001). EGFR is mainly a predictive factor for the prognosis of post-operative patients with TNM stage I-II colorectal cancer, and nm23 is important for predicting the prognosis of patients with stage III-IV, and EGFR and nm23 could be as predictor of combination.

Upregulation of programmed death ligand 1 and epidermal growth factor receptor is associated with poor prognosis in gastric cancer

Background: Programmed death ligand-1 (PD-L1) and epidermal growth factor receptor (EGFR) are both expressed on the surface of gastric cancer cells. We aimed to evaluate the relationships between protein expression levels and patient clinicopathologic characteristics as well as their prognostic impacts. Methods: The expression levels of PD-L1 and EGFR on tumor tissues and adjacent normal tissues were measured by immunohistochemistry in 90 cases of human gastric adenocarcinoma. The relationships of protein expression with clinicopathologic characteristics and prognosis were calculated by SPSS version 21. Results: PD-L1 and EGFR protein expression were upregulated in tumor tissues compared with adjacent normal tissues (P=0.036, P Conclusions: Our findings suggest that elevated expressions of PD-L1 and EGFR are prognostic factors for shorter overall survival respectively. Patients with co-expression of both tended to have worse prognosis.

MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by targeting ATOH1

The aim of the present study is to investigate the expression and function of miR-613 in colon cancer (CC) and illuminate the molecular mechanisms underlying miR-613-regulated CC progression. Our data demonstrated that miR-613 was upregulated in CC tissue samples (P = 0.009) and human CC cell lines (HCT-116 and Lovo; P = 0.001 and P = 0.003, respectively), which also promoted the proliferation, invasion and migration of CC cells (P < 0.05). The dual-luciferase reporter assay confirmed that Atonal homolog1 (ATOH1) was the target mRNA of miR-613. Rescue experiments showed that ATOH1 overexpression vector significantly reversed the stimulative effects of miR-613 mimic on the progression of HCT-116 and Lovo cells (P < 0.001). Positive ATOH1 expression in CC tissues was significantly associated with lower grade (χ2 = 3.592, P = 0.043), lower TNM stage (χ2 = 3.537, P = 0.048) and better overall survival (P=0.041). Jun N-terminal kinase 1 (JNK1) pathway and Mucin 2 (MUC2) were the potential downstream proteins of miR-613/ATOH1. miR-613 is an oncogene in CC and promotes the proliferation, invasion and migration of CC cells by targeting ATOH1 likely via activating JNK1 pathway and upregulating MUC2.

Expression of CCR6 in esophageal squamous cell carcinoma and its effects on epithelial-to-mesenchymal transition

Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis. We detected the expression of C-C motif chemokine receptor 6 (CCR6) and epithelial-to-mesenchymal transition (EMT) markers in esophageal tissues/cells, and evaluated the effects of CCR6 on ESCC cells proliferation, migration and invasion in response to C-C motif chemokine ligand 20 (CCL20) treatment. Our data showed CCR6 was highly expressed in ESCC cell lines (ECA-109 and TE-1), whereas kept in a low expression in normal cell lines HEEC (P < 0.001). CCL20 stimulus induced a significant decrease in the proliferation ability of ESCC (P < 0.05). The healing speed of CCL20 group was significantly higher than control in ECA-109 (P < 0.01), whereas significantly lower in αCCR6+CCL20 group than CCL20 group (P < 0.05).The number of cells permeabling through the polycarbonate membrane in CCL20 group was higher than control (P < 0.01). The cell number in αCCR6+CCL20 group was significantly reduced compared to CCL20 group in ECA-109 (P < 0.05). Moreover, after CCL20 stimulated in ECA-109, both mRNA and protein level of E-cadherin significantly decreased compared to control, while Vimentin was significantly higher. In αCCR6+CCL20 group, mRNA and protein level of E-cadherin significantly increased compared to CCL20 group, while Vimentin was much lower than CCL20 group. There was no significant difference in TE-1. In summary, high expression of CCR6 existed in the lymph node metastasis and TNM stage of ESCC. CCR6 play an important role in the regulation of tumor cell proliferation, invasion and migration. CCR6 may participate in regulating the occurrence of EMT in ESCC.