[Bioinformatics-based analysis of the effect of general Transcription Factor IIH on prognosis of Prostate cancer].

Objective: To investigate the genetic and expression characteristics of transcription factor IIH (TFIIH) in pre-initiationcomplex in prostate cancer (PCa) and its relationship with prostate cancer progression. Methods: Analyzing the expression characteristics and clinical signification of TFIIH subunits about 495 cases of PCa and 52 cases of adjacent cancer in The Cancer Genome Atlas-Prostate adenocarcinoma (TCGA-PRAD) database. PCa microarray chip was used to verify the correlation between the key factor General Transcription Factor IIH Subunit 4 (GTF2H4) in TFIIH and clinical features. Results: The 495 patients with PCa were (61.01±6.82) years old.The mRNA expression of ERCC3、GTF2H4 and MNAT1 were high in PCa tissues with GS≥8(P<0.05). The expression of GTF2H4 and MNAT1 were relevant to the pathological stages(P<0.05). High expression of GTF2H4 has higher biochemical recurrence (BCR) rate in PCa patients(HR=2.47, 95%CI:1.62-3.77, P<0.001), which has better predictive effect of BCR in PCa patients(The 3rd, 5th, and 7th year AUC all>0.7) than other subunits, and it has been verified in four additional databases. Single-factor Cox regression analysis showed that GTF2H4 were risk factors for BCR (HR=2.470, 95%CI:1.620-3.767, P<0.001) and GTF2H5 were protective factors(HR=0.506,95%CI: 0.336-0.762, P=0.001). The results of immunohistochemical staining showed that the protein expression of GTF2H4 was correlated with the clinical features of PCa patients.The differences of the above results were statistically significant. Conclusion: GTF2H4, the key factor of TFIIH, is highly expressed in PCa and indicates a poor prognosis.

Who are the real high-risk patients with pathological T2N0M0 non-small-cell lung cancer that can benefit from adjuvant chemotherapy?

BACKGROUND: The benefit of adjuvant chemotherapy (ACT) in pathological T2N0M0 non-small-cell lung cancer (NSCLC) patients is not clear. METHODS: One thousand and fifty pathological T2N0M0 NSCLC patients were included and divided into two groups: with and without ACT. A propensity score matching analysis was carried out to minimize selection bias. The significance of ACT in high-risk patients was further analyzed. The Kaplan-Meier method and Cox proportional hazards model were used to assess the impact of ACT on the overall survival (OS), disease-free survival (DFS), and cancer-specific survival. RESULTS: For the entire cohort, 31.9% (335/1050) of patients received ACT. After propensity score matching, 325 pairs of patients were matched. OS and DFS were comparable between groups in the original or matched cohort, which was confirmed by the multivariate analysis (all P > 0.05). In high-risk patients, the data suggest that ACT could improve OS and DFS only in patients with tumours >4 cm (OS: P = 0.003; DFS: P = 0.013). ACT could significantly improve the 5-year OS in patients with wild-type epidermal growth factor receptor (EGFR) (P = 0.022). ACT, however, could not improve cancer-specific survival in any subgroup, including patients with tumours >4 cm or wild-type EGFR (all P > 0.05). For patients with other high-risk factors, ACT failed to benefit patients in long-term outcomes. CONCLUSIONS: In resected pT2N0M0 NSCLC patients, those with tumours >4 cm and wild-type EGFR are real high-risk patients and could gain survival benefit from ACT. Further prospective study is needed to confirm the definition.

[Germline gene testing of the RET, VHL, SDHD and SDHB genes in patients with pheochromocytoma/paraganglioma].

OBJECTIVE: To analyze the germline variations of genes RET, VHL, SDHD and SDHB in patients with pheochromocytoma and/or paraganglioma and to evaluate variations of these genes in Chinese patients. METHODS: Patients who were treated in Peking University First Hospital from September 2012 to March 2014 and diagnosed with pheochromocytoma and/or paraganglioma by pathologists were included in this study. Twelve patients were included in total, of whom 11 had pheochromocytoma, and 1 had paraganglioma. Deoxyribonucleic acid (DNA) was extracted from the leukocytes of peripheral blood of the patients. The exons 10, 11, 13-16 of the RET gene, and all exons of VHL, SDHB and SDHD genes and their nearby introns (±20 bp) were amplified with polymerase chain reactions, and the products were sent to a biotechnology company for sequencing. The sequencing results were compared with wildtype sequences of these genes to identify variations. One of the patients was diagnosed with multiple endocrine neoplasia type 2A. A family analysis was performed in his kindred, and his family members received genetic tests for the related variations. RESULTS: Three patients were found to have germline gene variations. A c.136C>T (p.R46X) variation of the SDHB gene was found in a patient with malignant pheochromocytoma. A c.1901G>A (C634Y) variation, as well as c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were found in a patient with multiple endocrine neoplasia type 2A. After a family analysis, five family members of this patient were found to have the same variations. c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were also found in a clinical sporadic patient without evidence of malignancy. A patient with congenital single ventricle malformation and pheochromocytoma was included in this study, and no variation with clinical significance was found in the four genes of this patient. CONCLUSION: 25% (3/12) patients with pheochromocytoma or paraganglioma were found to have missense or nonsense germline gene variations in this study, including the c.136C>T (p.R46X) variation of the SDHB gene, the c.1901G>A (C634Y) variation of the RET gene, and c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene. The former two variations have already been confirmed to be pathogenic. The existence of these variations in Chinese patients with pheochromocytoma and/or paraganglioma was validated in this study, which supports the conclusion that genetic testing is necessary to be generally performed in patients with pheochromocytoma and/or paraganglioma.

MiR-222 promotes proliferation, migration and invasion of lung adenocarcinoma cells by targeting ETS1.

OBJECTIVE: The lung adenocarcinoma is a type of lung cancer. This research is to investigate the effects of miR-222 on the proliferation, migration and invasion of the lung adenocarcinoma cells. MATERIALS AND METHODS: At the beginning, MiR-222 and the controls were transfected to the lung adenocarcinoma cell line A549 for CCK-8 proliferation, transwell migration and Matrigel invasion, and then observed the effect of miR-222 on the proliferation, migration and invasion of lung adenocarcinoma cells. The miR-222 target was regulated by ETS1 downwards to participate in the regulation of the process by using the luciferase reporter assay, the Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and the Western blotting. RESULTS: According to CCK-8 proliferation assay, the Transwell migration and the Matrigel invasion assay, it discovered that MiR-222 can promote the proliferation, migration and invasion of the lung adenocarcinoma cells. Luciferase reporter assay, RT-qPCR and Western blot assay showed that miR-222 could regulate the expression of ETS1 downwards and ETS1 participated in the regulation of the process CONCLUSIONS: ETS1 promotes proliferation, migration and invasion of lung adenocarcinoma cells by targeting the regulated miR-222 downwards.

Effect of p53 gene polymorphism on functions of prostate cancer cells.

Prostate cancer cells were transfected with plasmids [empty plasmids, wild-type pcDNA3.1-p53 (V/V), mutant type pcDNA3.1- p53 (G/G)] to analyze the effect of p53 gene polymorphisms on the proliferation, cycle, and apoptosis of prostatic cancer cells. Empty plasmids containing wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1- p53 (G/G) were used to transfect PC3 and LNCaP cells, respectively. Cell proliferation was detected at 0, 24, 48, and 72 h using the MTT method. Cells were collected at 24 and 72 h. The distribution of cell cycles in various groups was detected using flow cytometry (propidium iodide staining method) and the apoptosis rate was detected using annexin V + propidium iodide double staining. Compared with the control group, wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G) showed a significant inhibitory effect on cell proliferation (P < 0.05); the inhibitory effect of the mutant type was stronger than that of the wild-type. There was no significant difference between PC3 cells and LNCaP cells. After transfection with wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G), PC3 and LNCaP cells were arrested in the G0/G1 stage. Transfection with pcDNA3.1-p53 (G/G) showed a more significant effect than transfection with pcDNA3.1-p53 (V/V). Both the wild-type pcDNA3.1-p53 (V/V) and mutant-type pcDNA3.1-p53 (G/G) led to an increased apoptosis rate of PC3 and LNCaP cells. The p53 gene polymorphism affects the proliferation, apoptosis, and cycle of prostate cancer cells and may serve as a reliable index for the diagnosis and treatment of prostate cancer.

Preoperative level of serum amyloid A is superior to C-reactive protein in the prognosis of esophageal squamous cell carcinoma.

Preoperative elevations in the levels of serum amyloid A (SAA) or C-reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative-intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1-, 3-, and 5-year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r(2) = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.

[Primary tracheal carcinoma--report of 5 patients].

From 1980 through 1985, 5 patients with primary tracheal carcinoma were admitted to Human Cancer Hospital, comprising 0.024% of total admissions during the same period. The incidence of lung cancer and laryngeal cancer was 386 and 43 times as high as that of tracheal carcinoma. All were proved pathologically. 3 patients were given radical operation, followed by radiotherapy; 1 received radiotherapy plus chemotherapy and the other, chemotherapy alone. All three patients treated by operation plus radiotherapy survived for more than 3 years and 2 of them are still alive. Diagnosis, causes and avoidance of misdiagnosis are discussed.