PurposeAccording to the WHO, the cribriform pattern is a subtype of acinar (Aci) predominance in invasive adenocarcinoma (ADC) of the lung. Recently, several studies have demonstrated poor prognosis in patients with cribriform predominance. This study was performed to examine the correlations of cribriform pattern with the clinicopathology, molecular features and prognosis in patients with invasive ADC.MethodsHistological subtypes were evaluated in 279 patients who underwent complete resection for invasive ADC. Patients of the Aci-predominant subtype were divided into two subgroups according to the percentage of cribriform cancer (≥5% vs <5%). Clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and molecular changes were compared. In addition, both OS and DFS were compared between patients with cribriform-predominant (n=33) and pure Aci-predominant (n=88) ADCs.ResultsA cribriform pattern was found in 111 (39.8%) cases and ranged from 5 % to 100 % of the total tumour volume (mean±SEM, 30%±2%). Of 117 patients with Aci predominance, 79 showed the cribriform pattern, while the remaining 38 did not. The cribriform pattern was associated with aggressive pathological behaviour, including advanced stages of cancer, nuclear atypia, mitoses, lymph node invasion, metastasis and larger tumour size. The subgroup with cribriform cancer (≥5%) had significantly poorer OS and DFS compared with the cribriform-negative (<5%) group. In addition, Cox multivariate analyses revealed that the cribriform pattern was an independent predictor of OS but not DFS. Moreover, OS was significantly lower in the cribriform-predominant group than in the Aci-predominant group.ConclusionThe cribriform pattern is associated with aggressive pathological behaviour and is an independent poor prognostic indicator in patients with Aci-predominant ADC of the lung.

Gliomas account for the highest cases of primary brain malignancies. Whereas previous studies have demonstrated the roles of CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) in various cancer types, its functions in lower grade gliomas (LGGs) remain elusive. This study aimed to profile the expression and functions of CKS2 in LGG. Multiple online databases such as The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), Gene Expression Profiling Interactive Analysis 2nd edition (GEPIA2), Tumor Immune Estimation Resource 2nd edition (TIMER2.0) as well as Gene Expression Omnibus (GEO) were used in this study. Immunohistochemistry (IHC) was performed to evaluate CKS2 protein expression. Our data demonstrated upregulation of CKS2 in LGG tissues at both mRNA and protein level, especially in grade III gliomas. Similarly, there was increased expression of CKS2 in isocitrate dehydrogenase 1 (IDH1) wildtype gliomas. In addition, increased DNA copy number and DNA hypomethylation might be associated with the upregulation of the CKS2 in LGG. Using the Kaplan-Meier survival analysis and the Cox regression analysis, CKS2 was shown to be independently associated with poor prognosis of LGG patients. Receiver operating characteristic (ROC) analysis revealed that CKS2 could effectively predict the 1-, 3-and 5-year survival rates of LGG patients. Enrichment analyses revealed that CKS2 was mainly involved in the regulation of the cell cycle in LGG. Taken together, our study demonstrated that CKS2 might be a candidate prognostic biomarker for LGG and could predict the survival rates of LGG patients.

The effect of the cytochrome P450 oxidoreductase (POR) rs10954732 (G > A) polymorphism on hepatocellular carcinoma (HCC) susceptibility is unknown. Here we found that A allele carriers showed a 69% decrease in susceptibility to HCC with overall survival (OS) prolonged to 199%, accompanied by lower activity for cytochrome P450 2E1. A total of 222 differentially expressed proteins were mainly enriched in neutrophil and T cell activation and involved in the immune and inflammatory responses, constituting the altered immune tumor microenvironment related with A allele by proteomics analysis. Hepsin (HPN) showed significant down-regulation in HCC and up-regulation in A allele carriers. A lower HPN level was associated with increased susceptibility to HCC and a worse prognosis. Moreover, HPN is a potential independent prognostic biomarker for HCC and is strongly associated with clinicopathological features, tumor-infiltrating status of immune cells both in our discovery cohort and database surveys. Our findings provide a new potential mechanism by which HPN may play an important role in the susceptibility of rs10954732 A allele carriers to HCC and their prognosis through tumor immune infiltration, thus offering potential insights for future studies on tumor immunotherapy.