Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis.

BACKGROUND: Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. METHODS: Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. RESULTS: In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. CONCLUSIONS: Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.

Expression of MTERF3 gene in breast carcinoma and the relationship with clinicopathological characteristics.

BACKGROUND: Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. It is a modular factor involves in mitochondrial ribosome biogenesis and protein synthesis. However, the association between MTERF3 and breast cancers remains largely unknown. The aim of this study was to investigate the expression of MTERF3 in breast carcinoma and to analyze its clinicopathological significance, and to examine the potential prognostic value of MTERF3 in breast cancer. METHODS: The protein expression levels of MTERF3 in MCF7 (Luminal A), BT-474 (Luminal B), SKBR3 (HER2 overexpression), MDA-MB-468 (Basal like) and MCF10A cell lines were detected by Western blotting. Immunohistochemistry (IHC), Western blotting, and semiquantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 58 breast cancer tissues and 58 noncancerous breast tissues. The MTERF3 expression data and clinical information from breast cancer patients were downloaded from the TCGA dataset by using the R3.6.1 software. Then the relationship between the expression level of MTERF3 and clinicopathological characteristics and the prognostic value was analyzed. A Cox regression model was performed for the multivariate analysis of the factors that affected the prognosis of breast cancer. The association between the expression levels of MTERF3 and other mitochondrial regulatory genes was analyzed with GEPIA. RESULTS: MTERF3 is upregulated in breast cancer cell lines compared to noncancerous breast cell line. The IHC results showed that the MTERF3 protein was located in the cytoplasm, and the rate of positive expression in breast cancer tissue was significantly upregulated compared with the adjacent normal tissue. The mRNA and protein expression levels of MTERF3 in breast cancer tissues were significantly higher than that in breast tissues. Moreover, the expression of MTERF3 was significantly correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site (P<0.05). Further analysis showed MTERF3 expression was not related to prognosis. Multivariate Cox regression analysis showed that age, metastasis status and tumor type were independent prognostic factors for breast cancer patients. The expression levels of MTERF3 were positively correlated with the TFAM, TFB1M, TFB2M, MTERF1, TEFM and MFN1 genes but negatively correlated with the MTERF4 and PINK1 genes. In addition, the expression levels of MTERF3 were not correlated with the MTERF2 gene. CONCLUSIONS: MTERF3 was significantly upregulated in breast cancer cells and tissues compared with noncancerous cells and tissues. Moreover, the expression level of MTERF3 was correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site. These findings suggested that the upregulation of MTERF3 may be used as a diagnostic and therapeutic target in breast carcinoma.

The effects of maternal cigarette smoking on pregnancy outcomes using assisted reproduction technologies: An updated meta-analysis.

There is strong evidence indicating that smoking has negative effects on female reproductive health. Studies to investigate the effects of female smoking on IVF outcomes have been conducted by several research groups, yet the results are controversial. To evaluate the impacts of female smoking on the outcomes of assisted reproduction, a meta-analysis was performed, which included studies published in English up to September 6, 2017 from the MEDLINE, EMBASE, and Cochrane library databases. Twenty-eight studies encompassing 5009 female smokers seeking assisted reproduction and 10,078 non-smokers were used in this meta-analysis. Significant negative outcomes were detected in the female smokers compared with non-smokers including decreases in live birth rate per cycle (OR=0.52, 95% CI 0.37-0.74), in clinical pregnancy rate per cycle (OR 0.59, 95% CI 0.51-0.68), in number of retrieved oocytes (MD=-0.87, 95% CI -1.39 to -0.25), and in average fertilization rate (MD=-4.80, 95% CI -8.49 to -2.02), as well as a significantly increased miscarriage rate per pregnancy (OR=2.48, 95% CI 1.79-3.43). In conclusion, the current meta-analysis provides compelling evidence that female smoking has a significantly negative impact on the outcomes of assisted reproductive technology (ART) and strongly recommends that female smokers will greatly benefit from a smoking cessation before employing ART to become pregnant.

Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection.

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) and characterized by covalently closed loop without 5' and 3' end. Recently, the diagnostic value of circRNAs has received more and more attention. However, the in-depth study about circRNAs diagnosis in breast cancer is still rarely reported. In present study, we try to investigate the circRNAs expression profiles in breast cancer peripheral blood and discover valuable diagnostic biomarkers. METHODS: The expression profiles of circRNAs in plasma specimens were screened from five breast cancer and paired healthy volunteer s. The expression levels of selected candidate circRNAs were detected by RT-PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve. RESULTS: CircRNAs microarray assay showed that 41 circRNAs were aberrantly expressed with 2 fold change, including 19 up-regulated and 22 down-regulated circRNAs. Among these circRNAs, 3 candidate circRNAs were validated to be significantly dysregulated using RT-PCR, including hsa_circ_0001785, hsa_circ_0108942 and hsa_circ_0068033. In lager study cohort (n=20), ROC curve showed that hsa_circ_0001785 had better diagnostic value (AUC=0.771) than others. Moreover, in further extensive study cohort (n=57), we found that hsa_circ_0001785 plasma had better diagnostic accuracy (AUC=0.784) than CEA (AUC=0.562) and CA15-3 (AUC=0.629). Besides, hsa_circ_0001785 plasma level was closely related to histological grade (P=0.013), TNM stage (P=0.008) and distant metastasis (P=0.016). Furthermore, hsa_circ_0001785 plasma level in postoperative patients (0.283±0.043) was significantly lower than that of preoperative patients (0.109±0.037, P<0.01). CONCLUSION: Our study reveals the aberrant circRNAs expression profiles in breast cancer peripheral blood, and identifies the potential diagnostic value of plasma hsa_circ_0001785, providing a stable biomarkers for the diagnosis and progress of breast cancer.