Expression and prognostic significance of NKD2 in ovarian cancer.

PURPOSE: Naked2 (NKD2) is a negative regulator of Wnt signaling pathway and associates with transforming growth factor secretion. The role of NKD2 in ovarian cancer is unknown. PATIENTS AND METHODS: Gene expression profiles were measured and compared in nine patients by RNA sequencing. NKD2 expressions in ovarian cancer were measured by reverse transcription polymerase chain reaction and western blot. Tissue slides of 79 patients were stained and scored for NKD2 expression. In vitro experiments were conducted to explore the role of NKD2 in ovarian cancer. The prognostic role of NKD2 was evaluated by survival analysis. RESULTS: NKD2 was upregulated in patients with better survival by mRNA and protein expression. Patients were classified as NKD2-high group (n = 30) and NKD2-low group (n = 49) according to immunohistochemical score. High NKD2 was correlated with lower recurrence rate (P = 0.002) and higher percentage of platinum-sensitive recurrence (P = 0.006). Median progression-free survival was significantly longer for NKD2-high patients than NKD2-low patients (49.1 vs.14.1 months, P < 0.001). Accordingly, there was a significantly difference in terms of overall survival time between two groups (hazard ratio: 3.04; 95% confidence interval: 1.58-5.85, P < 0.001). Multivariate regression suggested that NKD2 was independently prognostic factors in terms of progression-free survival (hazard ratio: 2.91; 95% confidence interval: 1.61-5.27, P < 0.001) and overall survival (hazard ratio: 3.6; 95% confidence interval: 1.80-7.21, P < 0.001). In vitro studies further demonstrated that NKD2 suppressed ovarian cancer cell proliferation, colony formation and cell migration. CONCLUSION: NKD2 is a novel prognostic marker and could suppress tumor progression in ovarian cancer.

Role of Lymphadenectomy During Interval Debulking Surgery Performed After Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer.

OBJECTIVE: The role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS. METHODS: We retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS. RESULTS: In 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease < 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease < 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS. CONCLUSION: Lymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients.

Diabetes has become a major public health concern worldwide, most of which are type 2 diabetes (T2D). The diagnosis of T2D is commonly based on plasma glucose levels, and there are no reliable clinical biomarkers available for early detection. Recent advances in proteome technologies offer new opportunity for the understanding of T2D; however, the underlying proteomic characteristics of T2D have not been thoroughly investigated yet. Here, using proteomic and glycoproteomic profiling, we provided a comprehensive landscape of molecular alterations in the fasting plasma of the 24 Chinese participants, including eight T2D patients, eight prediabetic (PDB) subjects, and eight healthy control (HC) individuals. Our analyses identified a diverse set of potential biomarkers that might enhance the efficiency and accuracy based on current existing biological indicators of (pre)diabetes. Through integrative omics analysis, we showed the capability of glycoproteomics as a complement to proteomics or metabolomics, to provide additional insights into the pathogenesis of (pre)diabetes. We have newly identified systemic site-specific N-glycosylation alterations underlying T2D patients in the complement activation pathways, including decreased levels of N-glycopeptides from C1s, MASP1, and CFP proteins, and increased levels of N-glycopeptides from C2, C4, C4BPA, C4BPB, and CFH. These alterations were not observed at proteomic levels, suggesting new opportunities for the diagnosis and treatment of this disease. Our results demonstrate a great potential role of glycoproteomics in understanding (pre)diabetes and present a new direction for diabetes research which deserves more attention.

Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial.

BACKGROUND: The Camrelizumab Plus Apatinib in Patients with Advanced Cervical Cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor camrelizumab plus the vascular endothelial growth factor receptor-2 inhibitor apatinib in patients with advanced cervical cancer. However, the predictive biomarkers for treatment outcomes are unknown. In this study, we aimed to identify potential predictors of treatment response in PD-1 inhibitor combination therapy. METHODS: Genomic profiling was performed on patients with available biopsy or surgical samples by targeted next-generation sequencing of 425 cancer-related genes in this preplanned, secondary analysis. Somatic alterations, including all non-synonymous mutations, and tumor mutational burden (TMB) were assessed for their predictive values in objective response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: A subset of 32 patients was included in this analysis. Top altered genes included PIK3CA (43.8%), STK11 (25%), FBXW7 (15.6%), and PTEN (15.6%). The PI3K/AKT pathway was among the most frequently dysregulated pathways, and its genetic alterations were identified in 68.8% of patients. PIK3CA (PFS HR 0.33, p=0.05; OS HR 0.23, p=0.04) and PTEN (PFS HR 3.71e-09, p=0.05; OS HR 3.64e-09, p=0.08) alterations were associated with improved outcomes. PI3K/AKT pathway genetic alterations showed improved predictive power compared with either PIK3CA or PTEN alterations alone (PFS HR 0.33, p=0.03; OS HR 0.25, p=0.02), while ERBB3 mutations (PFS HR 34.9, p<0.001; OS HR 19.8, p<0.001) correlated with poor survival. TMB-high (≥5 mut/Mb) was associated with prolonged PFS (HR 0.26, p<0.01) and OS (HR 0.31, p=0.05). Multivariate analysis showed ERBB3 mutations (PFS p=0.01, OS p<0.001), PD-L1 positive (PFS p=0.01, OS p=0.05), and high TMB (PFS p=0.01, OS p=0.05) remained significantly associated with survival. CONCLUSIONS: We uncovered that genetic alterations in PIK3CA, PTEN, ERBB3, and PI3K/AKT pathway, as well as TMB, could be novel predictive biomarkers in patients with cervical cancer treated with PD-1 inhibitor combination therapy. TRIAL REGISTRATION NUMBER: NCT03816553.

Respiratory Tract Infection: A Risk Factor for the Onset and Relapse of Adult-Onset Minimal Change Disease in Southern China.

AIMS/INTRODUCTION: Steroid resistance and frequent relapse are problems in the treatment of minimal change disease (MCD). However, epidemiological factors that influence steroid-resistant and relapse of MCD are rarely reported. This study evaluated potential factors that influence the onset and relapse of MCD and the epidemiological features of southern Chinese patients with adult-onset MCD. PATIENTS AND METHODS: Patients with adult-onset MCD were included from the Affiliated Hospital of Guangdong Medical University, which is located in the southernmost part of China's mainland, between 2015 and 2016. Potential influencing factors were investigated. RESULTS: Eighty-seven patients with incipient MCD were enrolled, and 85 of these patients were followed up; 71.8% (61/85) were steroid-sensitive and 28.2% (24/85) were steroid-resistant. In terms of seasonal distribution, the highest rate of incipient cases was in spring (39.1%, 34/87), which also showed a high rate of relapse cases (29.7%, 22/74). Among patients who were followed up for more than half a year and whose proteinuria completely resolved (69.4%, 59/85), 52.5% (31/59) were without relapse and 47.5% (28/59) were with relapse. Patients without relapse were older than those with relapse (P<0.05). Before disease onset, 20.7% (18/87) of patients with incipient MCD were diagnosed with infection, including 94.5% (17/18) with respiratory tract infection. Fourteen patients in complete remission posttreatment developed an infection before relapse, including 85.7% (12/14) with respiratory tract infection. CONCLUSION: Steroid resistance and frequent relapse are current challenges for the treatment of adult-onset MCD in southern China, and respiratory tract infection may be a risk factor for onset and relapse. Additionally, younger patients with MCD tend to have more frequent relapse.