Background: Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. Methods: From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. Results: C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. Conclusions: Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. Trial registration: ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.

Although ovarian cancer, a gynecological malignancy, has the highest fatality rate, it still lacks highly specific biomarkers, and the differential diagnosis of ovarian masses remains difficult to determine for gynecologists. Our study aimed to obtain ovarian cancer-specific protein candidates from the circulating small extracellular vesicles (sEVs) and develop a protein panel for ovarian cancer screening and differential diagnosis of ovarian masses. In our study, sEVs derived from the serum of healthy controls and patients with cystadenoma and ovarian cancer were investigated to obtain a cancer-specific proteomic profile. In a discovery cohort, 1119 proteins were identified, and significant differences in the protein profiles of EVs were observed among groups. Then, 23 differentially expressed proteins were assessed using the parallel reaction monitoring in a validation cohort. Through univariate and multivariate logistic regression analyses, a novel model comprising three proteins (fibrinogen gamma gene (FGG), mucin 16 (MUC16), and apolipoprotein (APOA4)) was established to screen patients with ovarian cancer. This model exhibited an area under the receiver operating characteristic curve (AUC) of 0.936 (95% CI, 0.888–0.984) with 92.0% sensitivity and 82.9% specificity. Another panel comprising serum CA125, sEV-APOA4, and sEV-CD5L showed excellent performance (AUC 0.945 (95% CI, 0.890–1.000), sensitivity of 88.0%, specificity of 93.3%, and accuracy of 89.2%) to distinguish malignancy from benign ovarian masses. Altogether, our study provided a proteomic signature of circulating sEVs in ovarian cancer. The diagnostic proteomic panel may complement current clinical diagnostic measures for screening ovarian cancer in the general population and the differential diagnosis of ovarian masses.

Baseline C-reactive protein (CRP) has been determined as a prognostic factor in nasopharyngeal carcinoma (NPC). This study was designed to further evaluate the impact of CRP kinetics on NPC patients. Thousand three hundred and seventy eight NPC patients from February 2001 to June 2011 were retrospectively reviewed. CRP were measured at beginning, middle, and the end of the treatment. The endpoints were overall survival (OS) and distant metastasis free survival (DMFS). Patients were divided into three groups according to baseline CRP and CRP kinetics: (1) continuously normal group: patients whose baseline CRP normal and never elevated, (2) ever-elevated group: patients whose CRP ever elevated regardless time points, (3) continuously elevated group: patients whose baseline CRP elevated and never normalized. Baseline CRP, CRP after treatment, and CRP kinetics were correlated with TNM stage, T stage, and N stage. Univariate and multivariate analysis identified that elevated baseline CRP and CRP after treatment had significant association with worse survival than normal CRP. Oppositely, elevated CRP during treatment was not associated with survival. Patients with continuously elevated CRP significantly had poor OS and DMFS (HR:2.610, 95%CI: 1.592–4.279, p < 0.001; HR:2.816, 95%CI: 1.486–5.302, p = 0.001, respectively). In multivariate analysis, CRP kinetics assessment is an independent prognostic factor for OS and DFMS in NPC patients (HR:2.512, 95%CI: 1.452–4.346, p = 0.001; HR:3.389, 95%CI: 1.734–6.625, p = 0.001, respectively). In conclusion, elevated CRP at baseline and after treatment are predictive factors of poor prognosis for NPC. The study of CRP kinetics shows that continuously elevated CRP during treatment might indicate an unfavorable prognosis for NPC.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon neoplasm arising from the olfactory mucosa. The optimal treatment regimen for ENB remains unclear. This study aims to evaluate its clinical features, long-term outcomes and explore optimal treatment patterns.

Background: The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC. Methods: We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018. Results: A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0–61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10–8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12–7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02–20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07–8.74, p = 0.038) predicted overall survival (OS). Conclusions: T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.