Cancer Biomarkers - Volume 21, issue 3

Authors: Ding, Dongbing | Yao, Yao | Yang, Changming | Zhang, Songbai

Article Type: Research Article

Abstract: The aim of present study was to investigate the clinical significances of mannose receptor (MR) and CD163 in colorectal cancer (CRC). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were utilized for this analysis. Preoperative serum MR and CD163 levels ranged from 0.153 to 0.804 μ g/ml (median = 0.359 μ g/ml) and from 0.319 to 1.314 μ g/ml (median = 0.685 μ g/ml) in CRC patients respectively. Strikingly, preoperative serum levels of MR and CD163 were significantly increased in CRC patients than in healthy individuals (P …< 0.0001). ROC analyses suggested that the optimum diagnostic cut-offs for serum MR and CD163 were 0.3485 μ g/ml (AUC 0.7205, sensitivity 54.82%, and specificity 80.46%) and 0.6111 μ g/ml (AUC 0.7463, sensitivity 62.65%, and specificity 80.46%) respectively. Detection of serum MR and CD163 together obviously enhanced the diagnostic accuracy (AUC 0.7968, sensitivity 69.28%, and specificity 77.01%). Then, preoperative serum MR and CD163 levels correlated significantly with serum CEA, CA19-9 and CA72-4 concentrations in CRC patients (P < 0.05). High MR and CD163 expression in serum was associated significantly with shorter overall survival (P < 0.05) and demonstrated as adversely prognostic factors (P < 0.05). Further, expression of MR and CD163 in CRC tissues was significantly higher than that in para-cancer tissues (P < 0.001). High expression of MR and CD163 in CRC tissues also correlated significantly with shorter overall survival (P < 0.05). MR and CD163 expression in serum or CRC tissues all correlated positively with the degree of lymphatic metastasis (P < 0.0001). In conclusion, MR and CD163 may be novel biomarkers for CRC patients. Show more

Keywords: Mannose receptor, CD163, marker, colorectal cancer

DOI: 10.3233/CBM-170796

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 689-700, 2018

Authors: Wang, Cheng-Yang | Ding, Huan-Zhang | Tang, Xiao | Li, Ze-Geng

Article Type: Research Article

Abstract: OBJECTIVE: The present study investigates the differences in immune function, hemorheological alterations and prognostic evaluation in colorectal cancer (CRC) patients with different traditional Chinese medicine (TCM) syndromes. METHODS: A total of 128 patients, diagnosed as stage II and III of CRC, were recruited. They were assigned into three TCM syndromes: deficiency syndrome, excess syndrome, and syndrome of intermingled deficiency and excess, and another 53 healthy individuals were selected as the control. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD + 3 , CD …+ 4 , CD + 8 , NK cells, and the ratios of CD + 4 /CD + 8 , Th1/Th2 and Tc1/Tc2). Whole blood viscosity (WBV), plasma viscosity (PV), hematocrit (Hct), erythrocyte sedimentation rate (ESR), plasma fibrinogen concentration (PFC) were measured using a fully-automatic blood rheological instrument. The univariate analysis and Cox regression analysis were conducted to evaluate the prognosis of CRC patients with different TCM syndromes. RESULTS: Compared with healthy individuals, CRC patients with three different syndromes had lower levels of CD + 3 , CD + 4 , NK cells, and ratios of CD + 4 /CD + 8 , Th1/Th2 and Tc1/Tc2, but higher level of CD + 8 , WBV, PV, Hct, ESR and PFC. Besides, patients with excess syndrome showed the highest levels of CD3 + , CD4 + and NK cells, and ratios of CD + 4 /CD + 8 , Th1/Th2 and Tc1/Tc2, but the lowest level of CD + 8 among three syndromes, and those with deficiency syndrome showed an opposite trend. Compared with patients with excess syndrome, those with deficiency syndrome showed decreased WBV, PV, Hct, ESR and PFC. The pathological type, surgical approach, tumor node metastasis (TNM) stage, liver metastasis, TCM treatment time and different TCM syndromes were independent factors of prognostic survival in CRC patients except perioperative blood transfusion volume. CONCLUSIONS: Taken together, we conclude that patients with TCM deficiency syndrome has lower immune function and poorer prognosis while patients with TCM excess syndrome has higher immune function and better prognosis of CRC. Show more

Keywords: Colorectal cancer, traditional Chinese medicine syndrome, immune function, hemorheological alteration, prognosis

DOI: 10.3233/CBM-170805

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 701-710, 2018

Authors: Lu, Hong-Jie | Yan, Jing | Jin, Pei-Ying | Zheng, Gui-Hong | Qin, Su-Ming | Wu, Dong-Mei | Lu, Jun | Zheng, Yuan-Lin

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''. The retraction notice is available at http://doi.org/10.3233/CBM229005.

Keywords: MicroRNA-152, CTSL, gastrointestinal stromal tumor, proliferation, migration, invasion, apoptosis

DOI: 10.3233/CBM-170809

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 711-722, 2018

Authors: Wang, Hui-Ju | Wang, Liang | Song, Shu-Shu | He, Xiang-Lei | Pan, Hong-Ying | Hu, Zhi-Ming | Mou, Xiao-Zhou

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Hypercalcemia is a potentially fatal and not rare complication of hepatocellular carcinoma (HCC), and its underlying mechanism remains unclear. Parathyroid hormone (PTH) is the most important regulator of the concentrations of calcium and phosphate in blood; parathyroid hormone-related protein (PTHrP) was the most frequent cause of humoral hypercalcemia of malignancy; parathyroid hormone 1 receptor (PTH1R) is the common receptor for PTH and PTHrP. The aim of this study is to investigate the expression of PTH, PTHrP, and PTH1R in HCC tissues, and their relationship with clinical pathological characters in HCC. METHODS: First, a …meta-analysis based on online Oncomine Expression Array database was conducted to compare the different mRNA expression of PTH1R, PTH and PTHrP between hepatocellular carcinoma and normal tissues. Then, the protein expression level of differentially expressed gene was examined by immunohistochemistry staining in 223 HCC tissues and 102 non-tumorous liver tissues controls. The relationship between the protein expression and clinicopathological parameters was analyzed by χ 2 test, and overall survival analysis was performed using Kaplan-Meier survival analysis. RESULTS: PTH1R mRNA expression was significantly lower in HCC tissues compared with normal tissues, while the expression of PTH and PTHrP showed no significant difference between HCC tissues and normal tissues. High PTH1R protein expression was found in 90/102 cases of adjacent non-tumorous liver tissues, and in 91 of 223 cases of HCC tissues. PTH1R expression was significantly related to tumor size, Edmondson Grade, AFP, and overall survival. CONCLUSIONS: PTH1R may be the major cause of hypercalcemia in HCC, and the decreased PTH1R expression was a poor prognosis in HCC. Show more

Keywords: PTH1R, PTH, PTHrP, hepatocellular carcinoma

DOI: 10.3233/CBM-170823

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 723-730, 2018

Authors: Petrini, Iacopo | Lencioni, Monica | Vasile, Enrico | Fornaro, Lorenzo | Belluomini, Lorenzo | Pasquini, Giulia | Ginocchi, Laura | Caparello, Chiara | Musettini, Gianna | Vivaldi, Caterina | Caponi, Sara | Ricci, Sergio | Proietti, Agenese | Fontanini, Gabriella | Naccarato, Antonio Giuseppe | Nardini, Vincenzo | Santi, Stefano | Falcone, Alfredo

Article Type: Research Article

Abstract: PURPOSE: The evaluation of molecular targets in gastric cancer has demonstrated the predictive role of HER2 amplification for trastuzumab treatment in metastatic gastric cancer. Besides HER2, other molecular targets are under evaluation in metastatic gastric tumors. However, very little is known about their role in resected tumors. We evaluated the expression of HER2, EGFR, MET, AKT1 and phospho-mTOR in resected stage II–III adenocarcinomas. METHODS: Ninety-two patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated. Antibodies anti-HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded slides. Using FISH, HER2 amplification was …evaluated in cases with an intermediate (+ 2) staining. RESULTS: EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p = 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p = 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was not a prognostic factor by itself (p = 0.234). AKT1 and EGFR overexpression was mutually exclusive and patients with EGFR or AKT1 overexpression experienced a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p = 0.005). CONCLUSIONS: EGFR is confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers. Show more

Keywords: Gastric cancer, gastro-esophageal junction cancer, EGFR, AKT1, MET

DOI: 10.3233/CBM-170865

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 731-741, 2018