Botulinum toxin type A in treating early-stage patients with small-angle acute acquired comitant esotropia.

AIM: To investigate botulinum toxin A (BTXA) efficacy on small-angle (≤25Δ) acute acquired concomitant esotropia (AACE) in early-stage patients. METHODS: The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study. A total of 72 small-angle AACE patients received BTXA extraocular muscle injection. Patients were grouped by onset-to-treatment time (Group A: ≤6mo, Group B: >6mo). Deviation of esotropia, eye alignment and stereopsis were analyzed at the period of pre/post-injection (1wk, 1, 3, and 6mo). Orthophoria rate at 6mo (horizontal deviation <10Δ and binocular single vision) were considered as outcome index. RESULTS: There were no significant baseline differences (P>0.05) between two groups except onset-to-treatment time (2mo vs 11mo, P<0.001). Higher orthophoria rates were in Group A at last follow-up (94.74% vs 73.53%, P=0.013). Post-BTXA deviations of two groups at 1mo showed no difference (P>0.05); while in 3 and 6mo Group A was significantly smaller than group B (all P<0.001). No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A. In Group B, deviation at 3mo (near: 2Δ vs 0, P<0.001; distance: 4Δ vs 0, P<0.001) and 6mo (near: 6Δ vs 0, P<0.001; distance: 6Δ vs 0, P<0.001) was significant increased compared to deviation at 1wk after treatment. Group A showed better stereopsis recovery in last follow-up compared to Group B (80″ vs 200″, P=0.002). Both groups obtained improved stereopsis after treatment (Group A: 80″ vs 300″, P<0.001; Group B: 200″ vs 300″, P=0.037). CONCLUSION: BTXA is effective for AACE with small deviation (≤25Δ) in early stage. Delayed treatment (>6mo) may reduce BTXA efficacy. Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

Synthesis of tetracyclic dibenzo[b,f][1,4]oxazepine-fused ß-lactams via visible-light-induced Staudinger annulation.

An efficient visible-light-induced Staudinger [2 + 2] annulation reaction between α-diazo ketones and dibenzo[b,f][1,4]oxazepine/thiazepine-imines under catalyst-free conditions has been developed. This protocol provides a facile method to synthesize tetracyclic dibenzo[b,f][1,4]oxazepine/thiazepine-fused ß-lactams bearing a quaternary carbon center with a broad substrate scope and high efficiency (37 examples, up to >99% yield).

Effects of slanted bilateral lateral recession vs conventional bilateral lateral recession on convergence insufficiency intermittent exotropia: a prospective study.

AIM: To observe the surgical effects of slanted bilateral lateral recession (S-BLR) versus conventional bilateral lateral recession (C-BLR) in convergence insufficiency intermittent exotropia (CI-IXT). METHODS: Using a randomized, double-blind, prospective design, 22 patients with CI-IXT who were admitted to Renmin Hospital of Wuhan University from July 2019 to December 2020 were included. Patients were randomly divided into either S-BLR or C-BLR group for their subsequent strabismus surgery. All patients were followed up for 12mo. Near deviation, distant deviation, and near-distance difference (NDD) were measured in all patients. RESULTS: Twelve months after surgery, NDD improvement was 10 (8, 13) prismatic degrees (PD) in S-BLR group and 3 (1, 6) PD in C-BLR group (P=0.011). The near deviation of S-BLR group was 0 (-2, 2) PD, while that of C-BLR group was -4 (-6, -3) PD (P=0.005). Before and after surgery, the difference in the distant deviation between the two groups was not statistically significant. There was no statistically significant difference in near stereopsis between the two groups (P=0.380) at 12mo. The success rate at 12mo after operation was 90.91% and 72.73% in the two groups (P=0.280). CONCLUSION: CI-IXT patients treated with S-BLR have better surgical outcomes than those treated with C-BLR, which indicates S-BLR is a safe and effective operation pattern.

XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7.

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.

[Updated studies on the immunotherapy of prostate cancer].

Prostate cancer (PCa) is a common urogenital malignancy in elderly men, for which current treatment strategies include surgery, radiotherapy, chemotherapy and androgen-deprivation therapy. However, PCa patients with recurrence or metastasis may ultimately develop therapeutic resistance. Recent studies show that PCa is an immunosensitive tumor and immunotherapy is a feasible option for its treatment, which involves therapeutic vaccination, immune checkpoint inhibitors, tumor microenvironment regulators, bi-specific antibodies, and adoptive cell metastasis. The application of immunotherapy, however, has been hindered by the adverse reactions of the patients and limited effects of single-drug medication. Individualized treatment and combination therapy are expected to be the alternatives in the development of the treatments of PCa.

Diagnostic value of thyroid micronodules with high b-value diffusion weighted imaging: Comparative study with high-resolution ultrasound.

PURPOSE: This study aims to compare the diagnostic performance of two imaging methods for thyroid nodules ≤1.0 cm and reduce unnecessary overdiagnosis. METHODS: A retrospective study was conducted on 80 patients with pathologically confirmed solitary thyroid micronodules underwent both high-resolution ultrasound (HRUS) and High b-value (2000 s/mm2) diffusion weighted imaging (DWI). Intra- and interobserver agreement (Intraclass correlation coefficient) was followed by Kruskal-Wallis test to detect whether the quantitative apparent diffusion coefficient (ADC) and thyroid nodule subgroups were related. Cohen's kappa analysis was applied to assess the interobserver consistency of DWI and HRUS characteristics. The receiver operating characteristic curves were adopted for evaluating the diagnostic performance of thyroid malignancy. The sensitivity, specificity, and accuracy of the two imaging methods were compared using the McNemar's test and Kappa test. RESULTS: A total of 80 patients were included, consisting of 43 malignant and 37 benign micronodules. The sensitivity, specificity and accuracy of DWI combined with rADC (ADCmin to ADCn ratio) for the diagnosis of thyroid micronodules were 83.7%, 89.2% and 86.3%, respectively. The area under the curve (AUC) was 0.91 (95% confidence interval [CI]: 0.84-0.97). The sensitivity, specificity and accuracy of HRUS diagnosis were 100%, 62.16% and 82.5%, respectively. CONCLUSION: High b-value DWI is superior to HRUS for evaluating the diagnostic performance of solid thyroid micronodules. DWI and its ADC quantitative analysis could be added to the evaluation of thyroid micronodules to improve the specificity of diagnosis, reduce overdiagnosis and avoid unnecessary biopsies or surgeries.

The therapeutic effects of earthworm extract on deep second-degree burn wound healing.

BACKGROUND: To investigated the effect of earthworm extract (EE) on deep second-degree burn wound healing process. METHODS: A burn wound model was created on the mice's skin and was subject to different treatments: the control group received no treatment; the Jingwanhong (JWH: a well-established, widely used external ointment for treating burn wounds) group was treated with 0.1 g of JWH cream and spray it on the wound surface; the EE group was treated with 0.1 mL of EE solution. All the mice were sacrificed at 3, 7, 11, and 15 days after injury (n=6/group/time point). Macroscopic observation, wound healing rate (WHR), wound healing time (WHT), water content (WC), hydroxyproline (Hyp) content, histological, and hematological analyses were performed at the burn wound sites. RESULTS: Better, faster burn wound healing in the JWH and EE groups than the control group at 15 days after injury were detected at the wound sites. Compared to the control group, the EE group had higher WHR, shorter WHT, lower WC, higher Hyp content, more fibroblasts, fibrocytes, and capillary endothelial cells; in addition, they showed greater capillary endothelial cell grouping at the wound sites during the healing process. This group also showed more platelets, white blood cells (WBCs), and neutrophilic granulocytes in serum at the early stages after burn injury. CONCLUSIONS: EE could effectively promote skin wound healing by decreasing edema, suppressing fibrosis, activating angiogenesis and epithelial regeneration, inhibiting scar formation, and reducing the risk of infection. Thus, it could be made into a promising healing agent for burn wound.

Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity.

Frequent outbreaks of viruses have caused a serious threat to public health. Previous evidence has revealed that DNA methylation is correlated with viral infections, but its role in innate immunity remains poorly investigated. Additionally, DNA methylation inhibitors promote IFN-I by upregulating endogenous retrovirus; however, studies of intrinsically demethylated tumors do not support this conclusion. This study found that Uhrf1 deficiency in myeloid cells significantly upregulated Ifnb expression, increasing resistance to viral infection. We performed whole-genome bisulfite sequencing and found that a single-nucleotide methylation site in the Ifnb promoter region disrupted IRF3 recruitment. We used site-specific mutant knock-in mice and a region-specific demethylation tool to confirm that this methylated site plays a critical role in regulating Ifnb expression and antiviral responses. These findings provide essential insight into DNA methylation in the regulation of the innate antiviral immune response.

Evaluation of Low-Dose Multidetector Computed Tomography Whole Gastroenterography With Oral Administration of Contrast Agents.

PURPOSE: To evaluate the degree of gastric, enteric, colonic, and rectal filling in multidetector computed tomography (MDCT) whole gastroenterography. METHODS: In this prospective study involving 124 patients, 78 and 46 patients underwent MDCT whole gastroenterography using positive and neutral oral contrast agents, respectively. The degree of filling of the stomach, small and large bowel, was qualitatively analyzed by experienced radiologists using a 3-point scoring system. RESULTS: The majority of patients received a score of ≥2 for small intestine filling using both positive and neutral contrast agents (90.5% and 78.2%, respectively), and <9% of the patients had a score of 0. The highest score for the degree of filling in the small intestine was observed in the ileum, followed by the duodenum and jejunum. There was a significant difference in the degree of filling achieved with positive and neutral contrast agents in the duodenum (P = .013) and jejunum (P = .047). More than 74% of cases had an optimal filling of the stomach, whereas >80% of the cases had an optimal filling of the colorectal segments. Only ≤5.1% had a score of 0 for the analyzed segments of the colorectum. Positive and neutral contrast agents were associated with similar degree of filling in the stomach and colon segments without a significant difference in the extent of contrast agent filling (P > .05). CONCLUSIONS: Multidetector computed tomography whole gastroenterography was found to be a simple, safe, noninvasive, painless, and effective modality for the diagnosis of stomach and bowel complications in clinical settings.

Balancing Dielectric Loss and Magnetic Loss in Fe-NiS2/NiS/PVDF Composites toward Strong Microwave Reflection Loss.

Lightweight, broad-band, and highly efficient microwave-absorbing materials (MAMs) with tunable electromagnetic properties are in high demand. However, the absorption properties are limited by the simple loss mechanism in commonly used absorbing materials. Here, we tested the microwave-absorbing properties of Fe-NiS2/NiS/poly(vinylidene fluoride) (PVDF) in the frequency range of 2-18 GHz. For the 2.5% Fe-NiS2/NiS/PVDF with the filling content of 20 wt %, the maximum reflection loss can reach -61.72 dB at 14.88 GHz, and the bandwidth can reach 3.8 GHz with the reflection loss value below -10 dB. Loss mechanisms of different composites were analyzed on the basis of their magnetic and dielectric properties using both experimental and computational methods. The results indicate that strong microwave absorption property is achieved through a balancing of dielectric loss and magnetic loss. These findings present a new strategy for the future design of MAMs.

Combination of serum gamma-glutamyltransferase and alkaline phosphatase in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis.

BACKGROUND: Gamma-glutamyltransferase (GGT) is one of the most important laboratory tests for the evaluation of liver damage. Through a long-term clinical observation of patients with secondary asymptomatic choledocholithiasis, we found that most patients had abnormal GGT serum levels. AIM: To investigate the combination of serum GGT and alkaline phosphatase (ALP) in predicting the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis. METHODS: In this retrospective cohort study, the clinical data of 829 patients with cholecystolithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from August 2014 to August 2017 were collected. Among these patients, 151 patients had secondary asymptomatic choledocholithiasis and served as the observation group, and the remaining 678 cholecystolithiasis patients served as the control group. Serum liver function indexes were detected in both groups, and the receiver operating characteristic (commonly known as ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS: The overall incidence of asymptomatic choledocholithiasis secondary to cholecystolithiasis was 18.2%. The results of liver function indexes including serum aspartate aminotransferase, alanine aminotransferase, direct bilirubin and total bilirubin levels showed no significant differences between the two groups (P > 0.05). However, the serum GGT and ALP levels were significantly higher in the observation group than in the control group (P < 0.05). The ROC curve analysis showed that the area under the curve was 0.881 (95%CI: 0.830-0.932), 0.647 (95%CI: 0.583-0.711) and 0.923 (95%CI: 0.892-0.953) for GGT, ALP, and GGT + ALP, respectively. The corresponding cut-off values of GGT and ALP were 95.5 U/L and 151.5 U/L, sensitivity were 90.8% and 65.1%, and specificity were 83.6% and 59.8%, respectively. The sensitivity and specificity of GGT + ALP were 93.5% and 85.1%, respectively. CONCLUSION: An abnormally elevated serum GGT level has an important value in the diagnosis of asymptomatic choledocholithiasis secondary to cholecystolithiasis. The combination of serum GGT and ALP has better diagnostic performance. As a convenient, rapid and inexpensive test, it should be applied in secondary asymptomatic choledocholithiasis routine screening.

Combined expression and prognostic significance of PPFIA1 and ALG3 in head and neck squamous cell carcinoma.

PPFIA family members and ALG3 play important roles in tumorigenesis and tumor progression. However, the exact roles of distinct PPFIA family members and ALG3 in head and neck squamous cell carcinoma (HNSCC) remain unclear. We studied the mRNA expressions of PPFIA family members and ALG3 in a variety of tumor types compared with the normal controls using the Oncomine database along with meta-analyses of their expressions in HNSCC cancer cell line. The mRNA expressions of PPFIA family members and ALG3 in laryngeal squamous cell carcinoma cell line and normal laryngeal cell line were detected by quantitative real-time polymerase chain reaction. Based on the cBioportal database, we further studied mRNA expression alterations and co-occurrence relationships of the PPFIA family members and ALG3 in HNSCC. The relationship between PPFIA1 and ALG3 mRNA expression alterations and prognoses in patients with HNSCC was explored. We found that PPFIA1 and ALG3 were distinctively overexpressed at the mRNA level in HNSCC tissues compared with normal tissues, they had a significant co-occurrence relationship, their mRNA expressions were significantly higher than other PPFIA family members in laryngeal squamous cell carcinoma cell line, and their mRNA expressions were also significantly higher in laryngeal carcinoma cell line than in normal laryngeal cell line. Patients without both PPFIA1 and ALG3 mRNA expression alterations had better overall survival and disease/progression-free survival compared with patients with both PPFIA1 and ALG3 alterations. Based on these findings, PPFIA1 and ALG3 may play roles in oncogene expression in HNSCC. Their combined overexpression is significantly associated with poor survival outcomes. The relationship between them and the mechanism of action in head and neck cancers deserve further investigation.

Diagnostic value of elevated serum carbohydrate antigen 199 level in acute cholangitis secondary to choledocholithiasis.

AIM: To investigate the diagnostic value of abnormal serum carbohydrate antigen 199 (CA199) level in acute cholangitis secondary to choledocholithiasis. METHODS: In this retrospective cohort study, the clinical data of 727 patients with choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from June 2011 to June 2017 were collected. Among these patients, 258 patients had secondary acute cholangitis and served as observation group, and the remaining 569 choledocholithiasis patients served as the control group. Serum liver function indexes and tumor markers were detected in both groups, and the receiver operating characteristic (ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS: The results of liver function tests showed no significant differences between the two groups (P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen, and alpha fetoprotein levels were also not significantly different (P > 0.05); however, the serum CA199 level was significantly higher in the observation group than in the control group (P < 0.05). The ROC curve analysis showed that the area under the curve was 0.885 (95%CI: 0.841-0.929) for CA199, and the cutoff value of 52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a specificity of 81.6%. CONCLUSION: Abnormally elevated serum CA199 level has an important value in the diagnosis of acute cholangitis secondary to choledocholithiasis. It may be a specific inflammatory marker for acute cholangitis.

The effect of earthworm extract on promoting skin wound healing.

Chronic nonhealing wounds pose a significant challenge to healthcare system because of its tremendous utilization of resources and time to heal. It has a well-deserved reputation for reducing the quality of life for those affected and represent a substantial economic burden to the healthcare system overall. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, there is paucity in data regarding its wound healing effects. Therefore, we investigated the effect of earthworm extract (EE) on skin wound healing process. The obtained data showed that EE has healing effects on local wound of mice. It decreased the wound healing time and reduced the ill-effects of inflammation as determined by macroscopic, histopathologic, hematologic, and immunohistochemistry parameters. The potential mechanism could be accelerated hydroxyproline and transforming growth factor-ß secretion-thus increasing the synthesis of collagen, promoting blood capillary, and fibroblast proliferation. It could accelerate the removal of necrotic tissue and foreign bodies by speeding up the generation of interleukin-6, white blood cells, and platelets. It thus enhances immunity, reduces the risk of infection, and promotes wound healing. All in all, the obtained data demonstrated that EE improves quality of healing and could be used as a propitious wound healing agent.

Study of analgesic effect of earthworm extract.

Pain represents a major clinical problem and one which has exercised generations of healthcare professionals. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, the analgesic effects of earthworm extract (EE) are seldom studied. Hence, we evaluated the analgesic effects of EE in mice. The obtained data showed that EE increased pain threshold and exhibited peripheral but not central analgesic effects in mice; evidenced by increased inhibition ratio in acetic acid writhing test and formalin test, whereas only slight increase in inhibition ratio in hot plate test and tail immersion test. In addition, EE decreased serum norepinephrine (NE), 5-hydroxytryptamine (5-HT), and nitric oxide (NO) synthase (NOS) concentration, similar to other analgesic drugs like morphine and aspirin. In a nutshell, the obtained data have demonstrated that EE has peripheral analgesic properties and could be used as a promising analgesic drug.

Identification of miR­124a as a novel diagnostic and prognostic biomarker in non­small cell lung cancer for chemotherapy.

Previous studies have suggested that dysregulation of microRNA (miR) -124a is associated with various types of human cancer. However, there are few studies reporting the level of miR­124a expression in non­small cell lung cancer (NSCLC). The present study investigated the association between miR­124a and NSCLC by analyzing the differential expression of miR­124a in NSCLC using the GEO database, as well as subsequently performing reverse transcription­quantitative polymerase chain reaction analysis on 160 NSCLC biopsies, 32 of which were paired with adjacent normal tissues. The results indicated that mir­124a expression levels were decreased in NSCLC tumor biopsies compared with adjacent normal tissues. The overall survival (OS) in patients with a high expression of miR­124a was prolonged relative to patients with low expression of miR­124a. The expression levels of miR­124a were associated with clinical characteristics, including lymph­node metastasis, tumor differentiation, tumor node metastasis (TNM) stage and diameter. Frequently, lymph­node metastasis, TNM stage, diameter and lack of chemotherapy have been associated with a worse prognosis in patients. In addition, the present study identified that high expression of miR­124awith chemotherapy may increase OS. In conclusion, the current study demonstrated that miR­124a was downregulated in NSCLC, and miR­124a was a potential prognostic tumor biomarker response to chemotherapy.

Association of the microsatellite (GT)n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma.

CONCLUSION: Long (GT)n repeat polymorphisms in the heme oxygenase-1 (HO-1) gene promoter and decreased serum HO-1 levels are associated with a higher susceptibility to laryngeal squamous cell carcinoma (LSCC). OBJECTIVE: In this case-control study, the association of HO-1 microsatellite (GT)n repeat polymorphisms and serum levels with the risk of LSCC was investigated. METHODS: A total of 142 LSCC patients, 54 vocal leukoplakia patients and 98 healthy controls, were examined for (GT)n polymorphisms by sequencing, and the serum HO-1 levels were detected in a sub-set from participants above by ELISA. RESULTS: Compared with the controls, the LSCC group had significantly higher frequencies of L-allele (> 29 repeats) and L-allele carriers (p < 0.001, OR = 2.037 and p = 0.005, OR = 2.152, respectively). The frequencies of lymph node metastasis and of moderate or poor differentiation were significantly higher in L-allele carriers compared to non-L-allele carriers (p < 0.05). Significantly lower serum HO-1 levels were detected in LSCC patients (p < 0.001), and patients with lower serum HO-1 levels had more advanced cancer stage and a higher lymph node metastasis rate (p < 0.05). Furthermore, the L-allele carriers had lower serum HO-1 concentrations compared with the non-L-allele carriers (p = 0.019).

Low expression of protocadherin7 (PCDH7) is a potential prognostic biomarker for primary non-muscle invasive bladder cancer.

Bladder cancer is a heterogeneous disease with outcome difficult to predict, and novel predictive biomarkers are needed. PCDH7, a member of protocadherins family, functions as tumor suppressor in several human cancers. The human PCDH7 gene is localized in chromosome 4p15, which is often inactivated in human cancers, including bladder cancer. The aim of this study was to investigate the clinical significance of PCDH7 expression in non-muscle invasive bladder cancer (NMIBC). PCDH7 expression was examined using immunohistochemical staining in 199 primary NMIBC tissues and 25 normal bladder epithelial tissues. Then the relationship between PCDH7 expression and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis was used to evaluate the correlation between PCDH7 expression and prognosis. PCDH7 expression in NMIBC tissues was significantly lower than that in normal bladder epithelial tissues (P < 0.001). Low PCDH7 expression correlated with advanced grade (P = 0.021) and larger tumor size (P = 0.044). Moreover, patients with low PCDH7 expression have shorter recurrence-free survival (P < 0.001), progression-free survival (P = 0.007) and overall survival (P = 0.011) than patients with high PCDH7 expression. Low PCDH7 expression is an independent predictor of recurrence-free survival (multivariate Cox analysis: P = 0.007), progression-free survival (multivariate Cox analysis: P = 0.014) and overall survival (multivariate Cox analysis: P = 0.004). The findings indicate that low PCDH7 expression is a potential prognostic biomarker for primary NMIBC.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy.

BACKGROUND Prostate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy. MATERIAL AND METHODS We evaluated the methylation status of PCDH17 in serum samples of 167 early-stage prostate cancer patients and 44 patients with benign prostatic hyperplasia (BPH) using methylation-specific PCR (MSP), and then evaluated the relationship between PCDH17 methylation and clinicopathologic features. Kaplan-Meier survival analysis and Cox analysis were used to evaluate its predictive value for BCR. RESULTS The ratio of PCDH17 methylation in prostate cancer patients was higher than in patients with BPH. Moreover, PCDH17 methylation was significantly associated with advanced pathological stage, higher Gleason score, higher preoperative PSA levels, and BCR. Kaplan-Meier survival analysis indicated that patients with methylated PCDH17 had shorter BCR-free survival time compared to patients with unmethylated PCDH17. Cox regression analysis indicated that PCDH17 methylation was an independent predictive factor for the BCR of patients after radical prostatectomy. CONCLUSIONS PCDH17 methylation in serum is a frequent event in early-stage prostate cancer, and it is an independent predictor of BCR after radical prostatectomy.