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Triple-negative breast cancer (TNBC) is a heterogeneous disease with an unfavorable prognosis and no specific targeted therapies. The role of non-SMC condensin I complex subunit D2 (NCAPD2), a regulatory subunit of the condensin I complex that mainly participates in chromosome condensation and segregation, has not been reported in cancer. We therefore evaluated the prognostic value and biological function of NCAPD2 in TNBC. The expression of NCAPD2 was studied in 179 TNBC tissues by immunohistochemistry, and associations among NCAPD2 expression, clinicopathologic features, and the prognosis information of patients with TNBC were analyzed. The mRNA expression profiles of 99 TNBC tissues were also studied, and cell biological behaviors were detected when NCAPD2 was altered in three TNBC cell lines. NCAPD2 expression was positively associated with lymph node metastasis (P = 3.84 × 10 -06 ), poor overall survival (P = 0.0033), and worse disease-free survival (P = 0.0013) of patients with TNBC. Moreover, knockdown of NCAPD2 might cause G 2 /M arrest through the p53 signaling pathway, which led to proliferation inhibition, polyploid cell production, and cell apoptosis and inhibited the invasiveness of TNBC cells. For the first time, we report the close association between NCAPD2 and cancer and demonstrate that NCAPD2 plays an important role in TNBC progression and acts as an independent poor prognostic factor and a potential therapeutic target for TNBC., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Breast cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast cancer subtype stratification., Methods: We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database., Results: The samples were gathered into three clusters following implementation of the t-SNE and DBSCAN algorithms and were categorized as 'hallmark-tsne' subtypes. Here, we identified a high-risk luminal A dominant breast cancer subtype (C3) that displayed increased motility, cancer stem cell-like features, a higher expression of hormone/luminal-related genes, a lower expression of proliferation-related genes and immune dysfunction. With regard to immune dysfunction, we observed that the motility-increased C3 subtype exhibited high granulocyte colony stimulating factor (G-CSF) expression accompanied by neutrophil aggregation. Cancer cells that produce high levels of G-CSF can stimulate neutrophils to form neutrophil extracellular traps, which promote cancer cell migration. This finding sheds light on one potential explanation for why the C3 subtype correlates with poor prognosis., Conclusions: The hallmark-tsne subtypes confirmed again that even the luminal A subtype is heterogeneous and can be further subdivided. The biological processes and immune heterogeneity of breast cancer must be understood to facilitate the improvement of clinical treatments.

Whether the heterogeneity in tumor cell morphology and behavior is the consequence of a progressive accumulation of genetic alterations or an intrinsic property of cancer-initiating cells established at initiation remains controversial. The hypothesis of biological predetermination in human cancer was proposed many years ago and states that the biological potency of cancer cells is predestinated in the precancerous stage. The present study aimed to investigate whether the aberrant molecular events occurring in initial cancer stages could eventually influence colorectal cancer (CRC) progression. We analyzed the mRNA and miRNA expression profiles of colorectal normal mucosa, low-grade intraepithelial neoplasia (LIN), high-grade intraepithelial neoplasia (HIN), and adenocarcinoma tissues. Compared with the transitions from LIN to HIN to invasive carcinoma, the transition from normal epithelium to LIN appeared to be associated with greater changes in the number and expression levels of mRNAs and miRNAs, with a differential expression of 2322 mRNAs and 71 miRNAs detected. Utilizing these early molecular changes, a miRNA-hub network analysis showed that 166 genes were identified as targets regulated by 30 miRNAs. Among these genes, a 55-gene signature regulated by 5 miRNAs was shown to be associated with overall survival or disease-free survival in three independent sample sets. Thus, the molecular changes in the transcriptome associated with the transition from normal to intraepithelial neoplasm may influence CRC progression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: Lung cancer patients within the pN0 category have a significantly different outcome. The aim of this study was to develop a mathematical model to assist in predicting the prognosis of pN0 lung squamous cell carcinoma (SCC)., Methods and Results: Twenty-three proteins were examined by immunohistochemical (IHC) analysis on primary tumour tissues from 319 lung SCC patients. In a training group, using IHC data, a recursive partitioning decision tree (RP-DT) was used to build a model for estimating the risk for lymphatic metastasis. This model was then validated in a test cohort. Of 23 proteins, 8 (matrix metallopeptidase 1, metalloproteinase inhibitor 1, Ras GTPase-activating-like protein IQGAP1, targeting protein for Xklp2, urokinase-type plasminogen activator, cathepsin D, fascin, polymeric immunoglobulin receptor/secretory component) were selected, and generated a tree model in a training group of 255 patients to classify them as at high or low risk of lymphatic invasion, with accuracy of 78.0% (compared to histopathological diagnosis), sensitivity of 83.0% and specificity of 70.3%. When the tree model was applied to the test group, the accuracy, sensitivity and specificity were 76.6%, 76.0% and 76.9%, respectively. The performance of this mathematical model was substantiated further in 34 'problematic' stage I/pN0 patients by survival analysis., Conclusions: The RP-DT model, constructed with eight protein markers for estimating lymphatic metastasis risk in pN0 lung SCC, is clinically feasible and practical, using IHC data from the primary tumour., (© 2011 Blackwell Publishing Limited.)

Matrix metalloproteinase-1 (MMP-1) participates in a variety of physiological and pathological processes. We previously found that MMP-1 was one of the lung cancer-related proteins detectable in peripheral blood. To validate our preliminary observations and explore the clinical significance of MMP-1 for lung cancer further, we carried out the present study. The concentrations of MMP-1 in circulating plasma specimens of 170 lung cancer patients and 70 healthy individuals were measured by an enzyme-linked immunosorbance assay. The expression status of the MMP-1 in archival tissue samples from 122 lung cancer patients was examined by immunohistochemical analysis. The correlation between the MMP-1 levels and prognosis of the lung cancer patients was then assessed statistically. Protein levels of MMP-1 were considerably raised in the plasma from lung cancer patients relative to those in healthy controls. The high plasma MMP-1 levels were associated with advanced-stage of the disease and significantly lower overall survival rate of the patients. Coincidently, MMP-1 protein extraordinarily overexpressed in the tumour tissues of lung cancer; and the up-regulated MMP-1 was associated with the progression (including tumour size, staging and lymphatic invasion), especially with decreased survival rate of the patients. Statistic analysis revealed that MMP-1 protein levels had an independent influence on survival. MMP-1 levels were elevated in both tumour tissue and blood; the latter may serve as an independent predictor for survival of lung cancer patients. MMP-1 protein levels in plasma/serum thus represent a potential and clinically relevant biomarker for the prognosis of patients with lung cancers., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)