Qin Jin

Aldehyde dehydrogenase 1 expression is correlated with poor prognosis in breast cancer

Abstract Breast cancer (BC) is one of the most common cancers worldwide, and is a major cause of death in women. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells and cancer stem cells, and its activity correlates with the outcome of various tumors, including BC. This study aimed to analyze the relationship between ALDH1 expression and clinicopathological characters in BC and the prognostic significance of ALDH1. We used quantitative reverse-transcription PCR (qRT-PCR) to detect ALDHA1 mRNA levels in 25 fresh frozen BC samples and matched noncancerous samples. Immunohistochemistry on tissue microarrays was used to analyze protein expression in 137 paraffin-embedded BC tissues and corresponding noncancerous tissues. STATA 16.0 software was used for statistical analysis. The results suggested that levels of both ALDH1 mRNA and protein in BC were significantly higher than in corresponding adjacent breast samples (3.856 ± 0.3442 vs 1.385 ± 0.1534, P < .001; 52.6% vs 25.5%, P < .001, respectively). ALDH1 protein expression was also significantly associated with histological grade (P  =  .017), tumor size (P  =  .017), and tumor–node–metastasis (TNM) stage (P  =  .038). Multivariate analysis using the Cox regression model demonstrated that ALDH1 expression (P  =  .024), molecular typing (P  =  .046), and TNM classification (P  =  .034) were independent predictive factors for the outcome of BC. Kaplan–Meier analysis and the log-rank test indicated that patients with high ALDH1 expression, triple-negative BC, and advanced TNM stage had a reduced overall survival time. These data suggest that ALDH1 could be used as a prognostic factor for BC and may provide a useful therapeutic target in the treatment of BC.

High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer

TMPRSS11D (HAT) belongs to the large type II transmembrane serine protease (TTSP) family, participating in various biological and physiological processes. TMPRSS11D expression has been reported during squamous cell carcinogenesis, however, its expression during non-small cell lung cancer (NSCLC) development has not been studied. In this study, we determined the mRNA and protein expression of TMPRSS11D in NSCLC tumorous and matched adjacent normal tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. TMPRSS11D protein expression in tumorous tissues were correlated with NSCLC patients’ clinical characteristics and overall survival. Both TMPRSS11D mRNA and protein expression levels were significantly higher in NSCLC tumorous tissues than in adjacent normal tissues. High TMPRSS11D protein expression was associated with high TNM stages, and high TMPRSS11D protein expression is an independent prognostic marker in NSCLC. Based on our results, we conclude that TMPRSS11D could play a role in NSCLC development and progression. Because of its role in proteolysis of extracellular matrix, targeting TMPRSS11D may prevent the development of metastasis in NSCLC.

LAMP1 expression is associated with poor prognosis in breast cancer

Lysosome associated membrane protein-1 (LAMP1) is a heavily glycosylated lysosomal membrane protein, which is able to protect the lysosomal membrane from intracellular proteolysis. LAMP1 has been implicated in cancer development and progression. However, LAMP1 expression in breast cancer (BC) and its relationship with the clinical parameters of BC has not yet been fully investigated. In the present study, LAMP1 expression in BC was characterized by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) on 20 pairs of fresh-frozen BC and corresponding non-cancerous tissues. In addition, tissue microarray immunohistochemistry (TMA-IHC) was conducted on 143 BC and matched non-cancerous tissue samples. The results of RT-qPCR and TMA-IHC demonstrated that LAMP1 expression in BC tissues was significantly higher than in corresponding non-cancerous tissues. Furthermore, LAMP1 protein expression levels were significantly associated with histological grade (P=0.047), estrogen receptor expression (P=0.003), progesterone receptor expression (P=0.002), molecular classification (P=0.022), lymph node metastasis (P=0.033) and tumor-node-metastasis (TNM) stage (P=0.012). Multivariate analysis using Cox regression models and Kaplan-Meier survival curves demonstrated that LAMP1 expression (P=0.037), molecular classification (P=0.017) and TNM stage (P=0.003) were independent prognostic factors for overall survival. The above data suggested that LAMP1 expression is associated with malignant attributes of BC and may serve as a novel prognostic factor for patients with BC.

EphA8 is a prognostic marker for epithelial ovarian cancer

EphA8 is one of the Eph receptors in the Eph/ephrin receptor tyrosine kinase (RTK) subfamily. During tumorigenesis, EphA8 is involved in angiogenesis, cell adhesion and migration. In this study, we determined the mRNA and protein expression levels of EphA8 in cancerous and normal ovarian tissue samples by quantitative reverse transcription PCR (qRT-PCR) (N = 60) and tissue microarray immunohistochemistry analysis (TMA-IHC) (N = 223) respectively. EphA8 protein levels in cancer tissues were correlated with epithelial ovarian cancer (EOC) patients’ clinical characteristics and overall survival. Both EphA8 mRNA and protein levels were significantly higher in EOC tissues than in normal or benign ovarian tissues (all P < 0.05). High EphA8 protein level was associated older age at diagnosis, higher FIGO stage, positive lymph nodes, presence of metastasis, positive ascitic fluid, and higher serum CA-125 level. High EphA8 protein level is an independent prognostic marker in EOC. We conclude that EphA8 acts as an oncogene in EOC development and progression. Detection of EphA8 expression could be a useful prognosis marker and targeting EphA8 represents a novel strategy for EOC treatment.

Reduced expression of EphA5 is associated with lymph node metastasis, advanced TNM stage, and poor prognosis in colorectal carcinoma.

Colorectal carcinoma (CRC) is the third most common cancer and a major cause of morbidity and mortality throughout the world. The prognosis of patients has improved markedly over the last 15 years because of the introduction of new therapy including molecular target drugs. To comprehensively understand the molecular process of carcinogenesis of colorectal carcinoma is essential for the diagnosis, prognosis and treatment. EphA5 is a member of the Eph family and plays a critical role in carcinogenesis of lung cancer, prostate cancer, and breast cancer. The expression profile and the role of EphA5 in colorectal carcinoma have not been well investigated till now. In this study, a set of colorectal carcinoma specimens was subjected to immunohistochemical assay using an EphA5 specific antibody. The relationship between the expression of EphA5 and clinicopathological parameters was statistically analyzed. EphA5 was positively expressed in all tested normal mucosa specimens (120/120, 100%) and partly in colorectal carcinoma specimens (70/120, 58.3%). The loss of EphA5 protein was associated with depth of wall invasion (P=0.002), poor tumor differentiation (P<0.001), lymph node metastasis (P<0.001), and advanced TNM stage (P<0.001). The survival analysis showed that patients with reduced expression of EphA5 had a poor overall survival (P=0.017). Our data indicate that EphA5 receptor may be a tumor suppressor in colorectal carcinoma and it may be a new therapeutic target for colorectal carcinoma.

Overexpression of FIBCD1 Is Predictive of Poor Prognosis in Gastric Cancer

Objectives Fibrinogen C domain containing 1 (FIBCD1) is a newly identified acetyl group recognition receptor. The aim of this study was to evaluate the prognostic significance of FIBCD1 in gastric cancer. Methods This study included 706 samples, and the clinical data of all patients were recorded in detail. We studied messenger RNA (mRNA) and protein expression of FIBCD1 in cancerous and normal tissues by quantitative real-time polymerase chain reaction (n = 54) and tissue microarray immunohistochemistry analysis (n = 706), respectively. Results mRNA and protein expression levels of FIBCD1 were significantly higher in gastric cancer than in normal tissues. High FIBCD1 protein level showed significant correlations with age (P = .011), TNM stage (P < .001), serum carcinoembryonic antigen (CEA) level (P = .002), and the expression of human epidermal growth factor receptor 2 (P < .001). Kaplan-Meier survival analysis revealed that patients with gastric cancer with high levels of FIBCD1 had a significantly shorter survival time than those with low expression levels. In univariate analysis, high FIBCD1 expression, older age, histologic type, differentiation, TNM stage, serum CEA, and serum CA19-9 level correlated with overall survival. Multivariate analysis suggested that FIBCD1 expression was an independent prognostic factor. Conclusions FIBCD1 may be a novel biomarker to evaluate the prognosis of gastric cancer.

Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells

Objectives Rab family members are key regulatory factors that function as molecular switches in multiple phases of vesicular trafficking. Our previous study demonstrated that Rab27A and Rab27B overexpression may predict a poor outcome of pancreatic ductal adenocarcinoma. The purpose of this study was to investigate the role of Rab27A and Rab27B in the progression of pancreatic cancer. Methods We down-regulated Rab27A and Rab27B expression in pancreatic cancer cell lines. The regulatory effects of knockdown Rab27A and Rab27B on pancreatic cancer cell were measured by cisplatin assay, invasion assay, proliferation assay, and Western blot assay. Results Rab27A and Rab27B down-regulation enhances sensitivity to cisplatin and induces apoptosis in ASPC-1 and PANC-1 cells. In addition, down-regulation of Rab27A reduced the invasive and proliferative ability of ASPC-1 cells, and Rab27B knockdown significantly prevented cancer invasion and proliferation in PANC-1 cells. Conclusions Our findings provide evidence that Rab27A and Rab27B play significant roles in cell invasion, proliferation, and apoptosis, as well as in chemotherapy resistance.

Automatic Immunoscoring of Immunohistochemistry Images of Human Lung Cancer Tissue Samples: A Screening Tool

Computer-aided image analysis of tissue sections is a modern accepted technique for tumor pathological diagnosis. With the advents of immunoscoring in tumor outcome evaluation, image-based immunoscore calculation has gained more and more attention. A new method of immunohistochemistry sections analysis, using the freeware ImageJ, is presented which can be applied to sections with either nuclear or cytoplasmic staining. The step-by-step process is presented and the method is tested using lung cancer tissues immunostained for cytokeratin 56, 18, NAPSIN, CGA, SYN, TTF, p63. This image analysis easily discriminates the positive staining and background, and quantified histogram profiles of the tested images, showing consistency with pathological diagnosis. The Spearman correlation between immunoscore and clinical TNM stage was 0.94. The method is easy to perform, without the need for previous image transformations. Further studies are needed to evaluate whether this method is efficient enough to be applied in clinical practice.