Combining serum peptide signatures with International Federation of Gynecology and Obstetrics (FIGO) risk score to predict the outcomes of patients with gestational trophoblastic neoplasia (GTN) after first-line chemotherapy.

Background: Gestational trophoblastic neoplasia (GTN) is a group of clinically rare tumors that develop in the uterus from placental tissue. Currently, its satisfactory curability derives from the timely and accurately classification and refined management for patients. This study aimed to discover biomarkers that could predict the outcomes of GTN patients after first-line chemotherapy. Methods: A total of 65 GTN patients were included in the study. Patients were divided into the good or poor outcome group and the clinical characteristics of the patients in the two groups were compared. Furthermore, the serum peptide profiles of all patients were uncovered by using weak cation exchange magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Feature peaks were identified by three machine learning algorithms and then models were constructed and compared using five machine learning methods. Additionally, liquid chromatography mass spectrometry was used to identify the feature peptides. Results: Multivariate logistic regression analysis showed that the International Federation of Gynecology and Obstetrics (FIGO) risk score was associated with poor outcomes. Eight feature peaks (m/z =1287, 2042, 2862, 2932, 2950, 3240, 3277 and 6626) were selected for model construction and validation by the three algorithms. Based on the panel combining FIGO risk score and peptide serum signatures, the neural network (nnet) model showed promising performance in both the training (AUC=0.9635) and validation (AUC=0.8788) cohorts. Peaks at m/z 2042, 2862, 2932, 3240 were identified as the partial sequences of transthyretin, fibrinogen alpha chain (FGA), beta-globin and FGA, respectively. Conclusion: We combined FIGO risk score and serum peptide signatures using the nnet method to construct the model which can accurately predict outcome of GTN patients after first-line chemotherapy. With this model, patients can be further classified and managed, and those with poor predicted outcomes can be given more attention for developing treatment failure.

Expression of PSCA, PIWIL1 and TBX2 and its correlation with HPV16 infection in formalin-fixed, paraffin-embedded cervical squamous cell carcinoma specimens.

The purpose of our study was to investigate the expression of prostate stem cell antigen (PSCA), piwi-like 1 (PIWIL1) and T-box 2 (TBX2) and its correlation with HPV16 infection in cervical squamous cell carcinoma (CSCC). HPV16 was detected by amplifying the HPV16 E7 gene by the polymerase chain reaction (PCR) method, and the expression of PSCA, PIWIL1, TBX2 and HPV16 E7 in 59 CSCCs and matched adjacent normal cervix (MANC) was examined by the streptavidin-peroxidase (SP) method. Fifty-two CSCCs and MANC specimens that were positive for the E7 gene and the E7 protein were identified as infected with HPV16 and included in present study. The rate of infection with HPV16 in CSCC was 52% (27/52), but that in matched adjacent normal cervix (MANC) samples was 4% (2/52). Infection with HPV16 was found to be statistically more frequent in CSCC (P = 0.000). The expression rates of PSCA, PIWIL1 and TBX2 in MANC were 6% (3/52), 8% (4/52) and 2% (1/52), respectively, but those in CSCC were 62% (32/52), 75% (39/52) and 52% (27/52), respectively. Higher expression rates of PSCA, PIWIL1 and TBX2 were observed in CSCC than in MANC (P = 0.000). HPV16 had a statistical positive correlation with PSCA, PIWIL1 and TBX2 in CSCC (P < 0.05). The increased expression of PSCA, PIWIL1 and TBX2 had no correlation with the patient's age or histological grade P > 0.05). The elevated expression of PSCA and PIWIL1 was associated with invasion of CSCC (P < 0.05). Up-regulated expression of TBX2 had a positive association with lymph node metastasis (P = 0.014). These findings demonstrate for the first time the expression of PSCA, PIWIL1 and TBX2 in CSCC. Their correlation with HPV16 might provide new basic information for investigating the molecular mechanism of HPV and help us to deepen our understanding of the interaction between HPV16 and host cells the carcinogenesis of CSCC.

Expression of PSCA, PIWIL1, and TBX2 in endometrial adenocarcinoma.

BACKGROUND: Endometrial cancer is the 4th most common gynecological cancer. The expression of prostate stem cell antigen (PSCA), piwi-like 1 (PIWIL1), and T-box 2 (TBX2) in endometrial cancer remains to be elucidated. MATERIAL AND METHODS: The expression of PSCA, PIWIL1, and TBX2 was examined using the streptavidin-peroxidase method in 64 endometrial endometrioid adenocarcinoma (EAC) and paired normal endometrium (NE) samples from the Shaanxi Province in China. RESULTS: Positive expression rates of PSCA, PIWIL1, and TBX2 were 75% (48/64), 25% (16/64), and 56% (36/64), respectively in EACs, but 5% (3/64), 6% (4/64), and 2% (1/64), respectively in NEs. The difference was statistically significant (p < 0.05). PSCA was positively correlated with TBX2 (p = 0.003) but not PIWIL1 (p = 0.188). PIWIL1 was positively correlated with TBX2 (p = 0.003). PSCA was positively correlated with age, tumor grade, and lymph node metastasis (p < 0.05). TBX2 had an association with lymph node metastasis (p = 0.014). PIWIL1 was not associated with clinicopathological features (p > 0.05). CONCLUSIONS: We report the first analysis of PSCA, PIWIL1, and TBX2 expression in EAC. Our findings suggest that PSCA and TBX2 might be candidate targets for cancer therapy, and have helped us further understand the carcinogenesis of endometrial cancer.

Expression pattern of the ASPP family members in endometrial endometrioid adenocarcinoma.

BACKGROUND: Apoptosis-stimulating protein of p53 (ASPP) family members can stimulate the apoptotic function of p53 but have no impact on its cell cycle arrest function. MATERIAL AND METHODS: The expression pattern of the ASPP family consisting of ASPP1, ASPP2, and iASPP was examined by immunohistochemistry in 45 formalin-fixed and paraffin-embedded endometrial endometrioid adenocarcinoma (EEA) specimens and 26 normal endometrial tissue (NET) samples. RESULTS: The expression rates of ASPP1 and ASPP2 in EEA were significantly lower than those in NET (p < 0.05). However, the iASPP expression rate in EEA was statistically higher in contrast to NET (p < 0.05). Expression of ASPP1 and iASPP in EEA had no correlation with any clinicopathological features (p > 0.05). iASPP was associated with grade, invasion, and lymph node metastasis (p < 0.05). CONCLUSIONS: It is a novel finding that the expression pattern of the ASPP family members has respective pathological and clinical implications in EEA, and iASPP might be a candidate target for EEA therapy.

The relationship between cyclooxygenase-2, CD44v6, and nm23H1 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the fourth most prevalent malignancy in China. The relationship between COX-2, CD44v6, and nm23H1 in esophageal squamous cell carcinoma (ESCC) remains unclear. MATERIAL AND METHODS: Expression of COX-2, CD44v6, and nm23H1 was examined, using the streptavidin-peroxidase method, in 82 ESCC and 30 normal esophageal mucosa (NEM) samples from the Shaanxi Province in China. RESULTS: The positive rates of COX-2, CD44v6, and nm23H1 were 73.2% (60/82), 64.6% (53/82), and 24.4% (31/82), respectively in ESCC, but 6.7% (2/30), 3.3% (1/30), and 90% (27/30), respectively in NEMs. There was a statistically significant difference between NEMs and ESCCs (p < 0.05). Expression of COX-2 showed a positive statistical correlation with expression of CD44v6 (r = 0.4732, p < 0.0001), and an inverse correlation with nm23H1 (r = -0.3226, p = 0.0035). Expression of COX-2, CD44v6, and nm23H1 had no significant correlation with gender or age (p > 0.05), but increased expression of COX-2 and CD44v6 showed statistical correlation with invasion and lymph node metastasis, respectively (p < 0.05). Decreased expression of nm23H1 was statistically correlated with lymph node metastasis (p = 0.0007) but had no correlation with invasion (p = 0.8221). CONCLUSIONS: This is the first report of a significant correlation between COX-2, CD44v6, and nm23H1 in ESCC. This knowledge might help us to further understand the molecular mechanisms of carcinogenesis and progression of ESCC.

Detection of human papillomavirus type 16 DNA in formalin-fixed, paraffin-embedded tissue specimens of gastric carcinoma.

OBJECTIVES: Human papillomavirus type 16 (HPV16) is regarded as one of the important tumor-related viruses, which are known to have a role in cervical carcinoma; however, there are few reports on HPV16 in gastric carcinoma (GC). Our study aimed to investigate the relationship between HPV16 and the occurrence of GC. METHODS: Liquid PCR (LPCR) and in-situ PCR (ISPCR) methods were carried out to detect the HPV16 oncogene E6 cell-type-specific enhancer in the long control region of HPV16 in 40 GCs and corresponding gastric adjacent normal mucosa (GANM). The patients were from Shaanxi Province in China; Helicobacter pylori (Hp) was detected by immunohistochemistry and by hematoxylin and eosin staining in their gastric tissues. RESULTS: The HPV16 E6 gene was detected in 37.5% (15/40) of the GCs and 5% (2/40) of the GANMs with LPCR, as was the cell-type-specific enhancer; however, the positive rate of E6 was 27.5% (11/40) in GCs and 0% (0/40) in GANMs, respectively, with ISPCR. HPV16 DNA was mainly located in the nucleus of gastric glandular epithelium cells. The infection rate of HPV16 DNA in GCs was higher than that in GANMs (P=0.0004), and the HPV16 had no statistical correlations with sex, age, invasion, grading or lymph node metastasis (P>0.05). The infection rate of HPV16 in cardiac GCs was significantly higher than that in noncardiac ones (P=0.0136), and HPV16 had no correlation with Hp in GCs (P=0.0829). Receiver operator characteristic curve analysis indicated that there was no statistical difference between the LPCR and ISPCR methods in our study through optimizing parameters in ISPCR procedures (P=0.768). CONCLUSIONS: These findings suggested that HPV16 can infect gastric glandular epithelium cells and that viral infection might play a role in the occurrence of GCs independent of or without the cooperation of an Hp infection.

Expression of ER, PR, C-erbB-2 and Ki-67 in Endometrial Carcinoma and their Relationships with the Clinicopathological Features.

BACKGROUND: To analyze the expression of estrogen receptors (ER), progesterone receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their relationships with the clinicopathological features. MATERIALS AND METHODS: Sixty-seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia endometrial samples were all selected in Shaanxi Provincial People's Hospital from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was respectively detected using immunohistochemical SP method. The relationships between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients' clinicopathological features as well as their correlations in EC tissue were also analyzed. RESULTS: The positive expression rates of ER and PR in EC tissue were 44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). The positive expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%, respectively, significantly higher than in atypical hyperplasia endometrial tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER and PR was closely associated with the differentiated degrees and depth of myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical staging, differentiated degrees, depth of myometrial invasion and presence or absence of lymph node metastasis (P<0.05). Spearman correlation analysis further displayed that the expression of ER was positively correlated with PR (r=0.393, P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329, P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67 (r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki-67 (r=0.342, P=0.005). CONCLUSIONS: Abnormal expression of ER, PR, C-erbB2 and Ki-67 might play an important role in endometrial malignant transformation and cell differentiation, so their joint detection is likely to be a comprehensive combination of immune factors, which is of great importance for EC prognosis.

The relationship between HPV16 and expression of cyclooxygenase-2, P53 and their prognostic roles in esophageal squamous cell carcinoma.

OBJECTIVES: This study aimed to investigate the relationship between human papillomavirus type 16 (HPV16) and expression of cyclooxygenase-2 (COX-2), P53 in esophageal squamous cell carcinoma (ESCC), which has not yet been elucidated. METHODS: HPV16 was detected by amplifying the HPV16 E6 gene by the PCR method, and the expression of COX-2, P53 protein in 69 ESCCs and 32 normal esophageal mucosa (NEM) from Shaanxi Province was examined by the streptavidin-peroxidase method. Estimation of overall survival by HPV16, COX-2, and P53 was calculated with the Kaplan-Meier method and analyzed with the log-rank test. RESULTS: The infection rate of HPV16 in ESCCs (35 of 69, 50.7%) was significantly higher than that in NEMs (two of 32, 6.25%) (P<0.01). The expression rate of COX-2 in ESCCs (44 of 69, 63.8%) was higher than that in NEMs (two of 32, 6.25%) (P<0.01). The expression intensity of COX-2 expression had statistical difference in histological grade (R = 0.4453, P = 0.0019), tumor stage (R = 0.438, P = 0.000), and metastasis (R = 0.417, P = 0.002). P53 expression rate was 49.3% (34 of 69) in ESCC and 18.8% (six of 32) in NEMs. The expression rate of P53 proteins in ESCC was statistically higher than that in N67EMs (P = 0.0037). The infection of HPV16 had inverse correlation with the overexpression of COX-2 in ESCCs (R = -0.321, P = 0.008). The HPV16 DNA in ESCC had no statistical correlation with P53 protein (R = -0.014, P = 0.9055) and the elevated expression of COX-2 had positive correlation with P53 protein in ESCC (R = 0.441, P = 0.000). No statistical correlation was observed between the infection of HPV16 and clinicopathological features in ESCCs including sex, age, tumor stage, and lymph node metastasis, respectively (P>0.05). The COX-2 had no statistical correlation with sex and age (P>0.05), but had association with tumor stage and lymph node metastasis, respectively (P<0.05). The expression of P53 protein had significant association with lymph node metastasis (P = 0.0005), but not with sex, age, and tumor stage, respectively (P>0.05). The overexpression of COX-2, infection of HPV16, and P53 protein in ESCC were not correlated with survival during the 5-year follow-up period (P>0.05). CONCLUSION: We first concluded that the increased expression of COX-2 had inverse correlation with HPV16 in ESCC. COX-2, HPV16, and P53 had no significant effect on the survival of patients with ESCC. These observations might help us to further understand the significant association between HPV16 and other molecules involved in the carcinogenesis and progression of ESCC.