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PubMed2005

Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers.

PURPOSE: The goal of this study was to determine whether distinct gene expression profiles are associated with intrinsic and/or acquired chemoresistance in epithelial ovarian carcinoma. EXPERIMENTAL DESIGN: Gene expression profiles were generated from 21 primary chemosensitive tumors and 24 primary chemo-resistant tumors using cDNA-based microarrays. Gene expression profiles of both groups of primary tumors were then compared with those of 15 ovarian carcinomas obtained following platinum-based chemotherapy ("post-chemotherapy" tumors). A theme discovery tool was used to identify functional categories of genes involved in drug resistance. RESULTS: Comparison of primary chemosensitive and chemo-resistant tumors revealed differential expression of 85 genes (P < 0.001). Comparison of gene expression profiles of primary chemosensitive tumors and post-chemotherapy tumors revealed more robust differences with 760 genes differentiating the two groups (P < 0.001). In contrast, only 230 genes were differentially expressed between primary chemo-resistant and post-chemotherapy groups (P < 0.001). Common to both gene lists were 178 genes representing transcripts differentially expressed between post-chemotherapy tumors and all primary tumors irrespective of intrinsic chemosensitivity. The gene expression profile of post-chemotherapy tumors compared with that of primary tumors revealed statistically significant overrepresentation of genes encoding extracellular matrix-related proteins. CONCLUSIONS: These data show that gene expression profiling can discriminate primary chemo-resistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identified that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions.

Adult↗

PubMed2006

Structured polychotomous machine diagnosis of multiple cancer types using gene expression.

MOTIVATION: The problem of class prediction has received a tremendous amount of attention in the literature recently. In the context of DNA microarrays, where the task is to classify and predict the diagnostic category of a sample on the basis of its gene expression profile, a problem of particular importance is the diagnosis of cancer type based on microarray data. One method of classification which has been very successful in cancer diagnosis is the support vector machine (SVM). The latter has been shown (through simulations) to be superior in comparison with other methods, such as classical discriminant analysis, however, SVM suffers from the drawback that the solution is implicit and therefore is difficult to interpret. In order to remedy this difficulty, an analysis of variance decomposition using structured kernels is proposed and is referred to as the structured polychotomous machine. This technique utilizes Newton-Raphson to find estimates of coefficients followed by the Rao and Wald tests, respectively, for addition and deletion of import vectors. RESULTS: The proposed method is applied to microarray data and simulation data. The major breakthrough of our method is efficiency in that only a minimal number of genes that accurately predict the classes are selected. It has been verified that the selected genes serve as legitimate markers for cancer classification from a biological point of view. AVAILABILITY: All source codes used are available on request from the authors.

Algorithms↗

PubMed2005

Molecular markers distinguish bone marrow mesenchymal stem cells from fibroblasts.

To characterize mesenchymal stem cells (MSC), we compared gene expression profiles in human bone marrow MSC (11 lines) and human fibroblasts (4 lines) by RT-PCR and real time PCR. Messenger RNA levels of MHC-DR-alpha, MHC-DR-beta, MHC-DR-associated protein CD74, tissue factor pathway inhibitor-2, and neuroserpin were much higher in MSC than in fibroblasts, even in the presence of large interindividual variations. Those of adrenomedullin, apolipoprotein D, C-type lectin superfamily member-2, collagen type XV alpha1, CUG triplet repeat RNA-binding protein, matrix metalloproteinase-1, protein tyrosine kinase-7, and Sam68-like phosphotyrosine protein/T-STAR were lower in MSC than in fibroblasts. FACS analysis showed that cell surface expression of MHC-DR was also higher in MSC than in fibroblasts. MHC-DR expression decreased after osteogenic differentiation, whereas the expression of adrenomedullin-a potent stimulator of osteoblast activity-along with collagen XV alpha1 and apolipoprotein D increased after osteogenic differentiation. The marker genes identified in this study should be useful for characterization of MSC both in basic and clinical studies.

Biomarkers↗

PubMed1999

[Gene expression profiles in squamous esophageal cancer tissues and adjacent almost normal tissues].

OBJECTIVE: To describe an esophageal cancer-specific expression profile and to identify genes that showed altered expression in squamous esophageal cancer tissues and their adjacent almost normal tissues. METHODS: The cDNA probes were synthesized from polyA(+)RNA of cancer and adjacent almost normal tissues and were differentially hybridized with two identical Atlas human cDNA expression arrays membranes containing 588 known genes. RESULTS: Autoradiographic analysis showed that of the 588 genes analyzed, 61 were found up-regulated in cancer, including cdc25B, Notch1, MMP, MET etc, and 22 down regulated in cancer, including cytokeratin4, BAD, IL-1 RECEPTOR ANTAGONIST, IL-6, etc. Expression levels of genes that associated with the regulation of cell proliferation, apoptosis, differentiation and metastasis altered most. CONCLUSION: The results for the first time provide an esophageal cancer-specific expression profile, showing that complex alterations of gene expression underlie the development of malignant phenotype of esophageal cancer cells. In addition, this line of research can lead to the identification of EC-specific genes which may be helpful for the development of diagnostic and prognostic biomarkers or therapeutic targets. The differential hybridization technique of Atlas Human cDNA expression array can be a useful method for describing the expression profiles of a tissue of cell interested.

DNA, Complementary↗

PubMed2004

Identifying progression-associated genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays.

Adult T-cell leukemia/lymphoma (ATL) is associated with human T-lymphotropic virus type-1 (HTLV-1). To understand the changes in expression that occur in the progression of chronic phase of ATL to acute crisis, the gene expression profiles of fresh ATL cells were compared in 4 pairs of samples (progression of chronic to acute phase in 3 patients, as well as 1 typical chronic phase sample vs. 1 typical acute phase sample) using high-density oligonucleotide DNA arrays. We identified 203 genes that were commonly upregulated in acute vs. chronic phase samples including ribosomal proteins, proteosome subunits, eukaryotic translation factors, immunophilins, heat shock proteins and genes important for DNA replication. Additionally, we identified 91 commonly downregulated genes including immune molecules related to MHC and a phosphatase. Several of the genes were previously identified to be associated with the Tax protein of HTLV-1. Some of the upregulated genes were located in amplified regions identified by comparative genomic hybridization in the corresponding chronic/acute ATL sample. Using real-time quantitative PCR, we confirmed the array-results in those specimens analyzed by microarray. These results demonstrated that distinct sets of genes that are known to be critical in cellular transformation and/or activation are up- or down-regulated during the transition to the acute phase of ATL.

Biomarkers, Tumor↗

PubMed2007

Heterologous tissue culture expression signature predicts human breast cancer prognosis.

BACKGROUND: Cancer patients have highly variable clinical outcomes owing to many factors, among which are genes that determine the likelihood of invasion and metastasis. This predisposition can be reflected in the gene expression pattern of the primary tumor, which may predict outcomes and guide the choice of treatment better than other clinical predictors. METHODOLOGY/PRINCIPAL FINDINGS: We developed an mRNA expression-based model that can predict prognosis/outcomes of human breast cancer patients regardless of microarray platform and patient group. Our model was developed using genes differentially expressed in mouse plasma cell tumors growing in vivo versus those growing in vitro. The prediction system was validated using published data from three cohorts of patients for whom microarray and clinical data had been compiled. The model stratified patients into four independent survival groups (BEST, GOOD, BAD, and WORST: log-rank test p = 1.7x10(-8)). CONCLUSIONS: Our model significantly improved the survival prediction over other expression-based models and permitted recognition of patients with different prognoses within the estrogen receptor-positive group and within a single pathological tumor class. Basing our predictor on a dataset that originated in a different species and a different cell type may have rendered it less sensitive to proliferation differences and endowed it with wide applicability. SIGNIFICANCE: Prognosis prediction for patients with breast cancer is currently based on histopathological typing and estrogen receptor positivity. Yet both assays define groups that are heterogeneous in survival. Gene expression profiling allows subdivision of these groups and recognition of patients whose tumors are very unlikely to be lethal and those with much grimmer outlooks, which can augment the predictive power of conventional tumor analysis and aid the clinician in choosing relaxed vs. aggressive therapy.

Animals↗

PubMedDate not supplied

A comparison of pollutant biomarker responses with transcriptional responses in European flounders (Platicthys flesus) subjected to estuarine pollution.

European flounders from two UK estuaries with different contaminant profiles were sampled and analysed for impacts of PAHs, heavy metals and estrogenic compounds by currently adopted measurement procedures used in statutory monitoring programs. These showed that fish from the polluted Tyne estuary had responded to all three classes of pollutants with elevations in hepatic EROD, MT and plasma VTG and that there was considerable interanimal variation in the magnitude of the response. Analysis of PAH metabolites in bile showed recent uptake of low molecular weight PAHs. The pollutant response was also apparent when hepatic levels of cytochrome P450 1A (CYP1A), metallothionein (MT) and vitellogenin (VTG) mRNAs were quantified by real time PCR. Whilst there did not appear to be a direct correlation between levels of gene transcripts and their protein products on an individual basis, these results demonstrate that measurements of mRNA levels of specific genes, or their protein products both demonstrate induction in polluted environments and are thus valid measures in biomonitoring studies. Procedurally, the use of the single generic technology of Q-PCR was much simpler and is worth pursuing in future studies.

Animals↗

PubMed2026

Integrated Clinicopathologic and Multiomic Profiling Reveals MEIS1-Rearranged Sarcoma as a Distinct Entity With 2 Prognostic Subgroups.

Sarcomas with MEIS1 fusions represent a rare, recently recognized group of mesenchymal neoplasms with a predilection for genitourinary and gynecologic sites. A subset exhibits skeletal muscle differentiation resembling spindle cell rhabdomyosarcoma. Existing literature is limited to case reports and small series, with scant comprehensive clinicopathologic, molecular, and outcome data. In this study, we analyzed a multi-institutional cohort of 20 MEIS1-rearranged sarcomas using integrated clinicopathologic review, genomic profiling, and DNA methylation analysis. The tumors occurred in 17 females and 3 males (median age, 41 years; range, 6-58 years), arising mainly in the uterus/vagina (n = 12), vulva/perineum (n = 4), bone (n = 2), and kidney (n = 2), with a median size of 9 cm (range, 2.5-20 cm). Histology showed mostly bland spindle cells in fascicles/storiform patterns, alternating cellularity, fibromyxoid stroma, prominent vascularity, and adipose metaplasia (45%). A subset of cases featured high-grade morphology with epithelioid cells and increased mitotic activity. Skeletal muscle markers were variably positive in 9 cases. Fusions involved MEIS1 with NCOA2 (16/20), NCOA1 (3/20), or FOXO1 (1/20). Recurrent additional genomic alterations included CTNNB1 mutations (31.6%) and MDM2 amplification (15%). DNA methylation profiling showed that MEIS1-rearranged sarcomas formed a unifying cluster comprising 2 subgroups, regardless of rhabdomyosarcomatous phenotype, clearly separated from other mesenchymal neoplasms, including various rhabdomyosarcoma subtypes and uterine sarcomas. The 2 DNA methylation (Meth) subgroups correlated with differences in genome-wide copy number variation (CNV) status (Meth-CNV high vs Meth-CNV low), with Meth-CNV high tumors characterized by high mitotic rate, frequent tumor necrosis, recurrent co-occurring CTNNB1 and MDM2 alterations, and recurrent chromosomal arm-level changes. Most importantly, this subgroup exhibited significantly worse overall survival (P = .027) and disease-free survival (median, 5 vs 99 months; P = .017). This study establishes MEIS1-rearranged sarcoma as a distinct entity with generally indolent but potentially aggressive behavior. The 2 methylation/CNV subgroups provide potential utility for prognostic stratification and highlight actionable molecular targets in high-risk cases.

Humans↗

PubMed2004

Truncal fat mass as a contributor to inflammation in end-stage renal disease.

BACKGROUND: An activated inflammatory response is a common feature of end-stage renal disease (ESRD) and predicts outcome. Adipose tissue is an endocrine organ that may contribute to an inflammatory burden by secreting adipocytokines such as interleukin 6 (IL-6). OBJECTIVE: The objective was to relate plasma concentrations of IL-6 in ESRD patients to body composition, regional fat mass distribution, and blood lipid profiles. DESIGN: One hundred ninety-seven ESRD patients (123 men; +/- SE age: 52 +/- 1 y) were evaluated shortly before dialysis started. Lean body mass and truncal and nontruncal fat mass were estimated by dual-energy X-ray absorptiometry. Nutritional status was evaluated on the basis of subjective global assessment and handgrip strength. Inflammatory biomarker and blood lipid concentrations were also evaluated. RESULTS: Median IL-6 (8.5 compared with 4.5 pg/mL; P < 0.001) concentrations were significantly greater in malnourished than in well-nourished patients. Moreover, negative correlations were observed between IL-6 and serum creatinine (rho = -0.19, P < 0.01), handgrip strength (rho = -0.24, P < 0.001), and serum albumin (rho = -0.34, P < 0.001). A significantly higher truncal fat mass (12.8 +/- 0.7 compared with 10.5 +/- 0.4 kg; P < 0.005) was observed in ESRD patients with inflammation (C-reactive protein >/= 10 mg/L). Inverse correlations were observed between plasma IL-6 and HDL cholesterol (rho = -0.16, P < 0.05) and apolipoprotein A (rho = -0.23, P < 0.001). CONCLUSIONS: Plausible relations exist between inflammatory biomarkers, such as IL-6 and high-sensitivity C-reactive protein, and regional fat distribution in ESRD patients. Moreover, the strong inverse relations between HDL cholesterol and apolipoprotein A and biomarkers of inflammation suggest that the chronic inflammatory response observed in ESRD patients is an important contributor to the atherogenic lipoprotein profile in uremia.

Absorptiometry, Photon↗

PubMed2002

Molecular profiling of angiogenesis markers.

The goal of this study was to develop a sensitive, simple, and widely applicable assay to measure copy numbers of specific mRNAs using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and identify a profile of gene expression closely associated with angiogenesis. We measured a panel of nine potential angiogenesis markers from a mouse transgenic model of prostate adenocarcinoma (TRAMP) and a mouse skin model of vascular endothelial growth factor (VEGF)-driven angiogenesis. In both models, expression of VEGF correlated with expression of mRNAs encoding other angiogenic cytokines (angiopoietin-1 and angiopoietin-2), endothelial cell receptor tyrosine kinases (Flt-1, KDR, Tie-1), and endothelial cell adhesion molecules (VE-cadherin, PECAM-1). Relative to control, in dermis highly stimulated by VEGF, the Ang-2 mRNA transcript numbers increased 35-fold, PECAM-1 and VE-cadherin increased 10-fold, Tie-1 increased 8-fold, KDR and Flt-1 each increased 4-fold, and Ang-1 increased 2-fold. All transcript numbers were correspondingly reduced in skin with less VEGF expression, indicating a relationship of each of these seven markers with VEGF. Thus, this study identifies a highly efficient method for precise quantification of a panel of seven specific mRNAs that correlate with VEGF expression and VEGF-induced neovascularization, and it provides evidence that real-time quantitative RT-PCR offers a highly sensitive strategy for monitoring angiogenesis.

Adenocarcinoma↗

PubMed2026

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans↗

PubMed2005

A Nuclear Receptor Atlas: 3T3-L1 adipogenesis.

The differentiation of a preadipocyte into a mature adipocyte represents a fundamental process in biology that requires a scripted program of transcriptional events leading to changes in gene expression. As part of our contribution to the Nuclear Receptor Signaling Atlas (NURSA), we used quantitative real-time PCR to profile the temporal expression of all 49 members of the mouse nuclear receptor superfamily at selected time points during differentiation of 3T3-L1 cells into mature, lipid-bearing adipocytes using two differentiation inducers [DMI (a cocktail of dexamethasone, 3-isobutyl-1-methylxanthine, and insulin) and rosiglitazone]. We also included a comparative analysis of nuclear receptor expression in mouse primary preadipocytes and mature adipocytes. In addition to confirming the expression of receptors known to be required for adipogenesis, this analysis revealed the existence of a tightly regulated transcriptional cascade that appeared in three distinct temporal phases. The first phase began within 4 h of adipogenic initiation with the transient, sequential expression of four previously uncharacterized receptors, followed by biphasic expression of a second subset, and ended with the sequential increase in a third receptor subset over a period of 2 wk after initiation. The discovery that these receptors may serve as adipogenic biomarkers and as potential therapeutic targets in adipose-related diseases highlights the utility of quantitative expression profiling as a method for directing mechanism-based approaches to study complex regulatory pathways.

3T3-L1 Cells↗

PubMed2006

Gene expression profiles and B-type natriuretic peptide elevation in heart transplantation: more than a hemodynamic marker.

BACKGROUND: B-type natriuretic peptide (BNP) is chronically elevated in heart transplantation and reflects diastolic dysfunction, cardiac allograft vasculopathy, and poor late outcome. This investigation studied peripheral gene expression signatures of elevated BNP concentrations in clinically quiescent heart transplant recipients in an effort to elucidate molecular correlates beyond hemodynamic perturbations. METHODS AND RESULTS: We performed gene microarray analysis in peripheral blood mononuclear cells of 28 heart transplant recipients with clinical quiescence (absence of dyspnea or fatigue; normal left ventricular ejection fraction [EF >55%]; ISHLT biopsy score 0 or 1A; and normal hemodynamics [RAP <7 mm Hg, PCWP < or = 15 mm Hg, and CI > or = 2.5 L/min per m2]). BNP levels were performed using the Triage B-type Natriuretic Peptide test (Biosite Diagnostics Inc, San Diego, Calif) and median BNP concentration was 165 pg/mL. Seventy-eight probes (of 7370) mapped to 54 unique genes were significantly correlated with BNP concentrations (P<0.001). Of these, the strongest correlated genes (P<0.0001) were in the domains of gelsolin (actin cytoskeleton), matrix metallopeptidases (collagen degradation), platelet function, and immune activity (human leukocyte antigen system, heat shock protein, mast cell, and B-cell lineage). CONCLUSIONS: In the clinically quiescent heart transplant recipient, an elevated BNP concentration is associated with molecular patterns that point to ongoing active cardiac structural remodeling, vascular injury, inflammation, and alloimmune processes. Thus, these findings allude to the notion that BNP elevation is not merely a hemodynamic marker but should be considered reflective of integrated processes that determine the balance between active cardiac allograft injury and repair.

Aged↗

PubMedDate not supplied

Profiling of Hodgkin's lymphoma cell line L1236 and germinal center B cells: identification of Hodgkin's lymphoma-specific genes.

The malignant cells of classical Hodgkin's lymphoma (cHL), Hodgkin and Reed-Sternberg (HRS) cells, appear to be derived from germinal center (GC) B cells in most cases of the disease. Apart from recent findings of constitutive activation of some transcription factors and autocrine stimulation by cytokine receptors, the mechanisms of malignant transformation in cHL still remain poorly understood. We performed a large scale gene expression study using serial analysis of gene expression (SAGE), comparing the cHL cell line L1236 and human GC B cells. Semiquantitative RT-PCR was used to confirm results from the SAGE and to analyze gene expression in 3 additional cHL cell lines. To investigate expression of some genes in cHL cases, we applied RT-PCR on microdissected HRS cells. In total, 464 genes showed a change in expression level of 5-fold or higher. For 12 genes (out of 177) identified as upregulated in L1236 cells, RT-PCR confirmed the SAGE results and also showed elevated expression in 3 other cHL cell lines. For 3 of the upregulated genes, expression by HRS cells in the tissue also was confirmed. Several of the differentially expressed genes may play a role in the pathogenesis of cHL because they represent potential oncogenes, such as rhoC, L-myc, and PTP4A, or transcription factors, such as ATF-5, ATBF1, and p21SNFT. The genes that showed significantly deregulated expression in HRS cells should be helpful not only for the identification of genes involved in the pathogenesis of cHL but also for discovering potential prognostic markers or therapeutic targets.

B-Lymphocytes↗

PubMed2003

Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.

Adolescent↗

PubMed2006

MALDI-TOF serum protein profiling for the detection of breast cancer.

BACKGROUND: Proteomic expression profiling has been suggested as a potential tool for the early diagnosis of cancer and other diseases. The objective of our study was to assess the feasibility of this approach for the detection of breast cancer. MATERIALS AND METHODS: In a randomized block design pre-operative serum samples obtained from 78 breast cancer patients and 29 controls were used to generate high-resolution MALDI-TOF protein profiles. The spectra generated using C8 magnetic beads assisted mass spectrometry were smoothed, binned and normalized after baseline correction. Linear discriminant analysis with double cross-validation, based on principal component analysis, was used to classify the protein profiles. RESULTS: A total recognition rate of 99%, a sensitivity of 100%, and a specificity of 97.0% for the detection of breast cancer were shown. The area under the curve of the classifier was 98.3%, which demonstrates the separation power of the classifier. The first 2 principal components account for most of the between- group separation. CONCLUSIONS: Double cross-validation showed that classification could be attributed to actual information in the protein profiles rather than to chance. Although preliminary, the high sensitivity and specificity indicate the potential usefulness of serum protein profiles for the detection of breast cancer.

Adult↗

PubMed2026

Prognostic value of genes associated with metastasis and propionate metabolism in rectal cancer.

BACKGROUND: Research indicates that alterations in propionate metabolic pathways play a critical role in cancer development and invasion. Postoperative metastatic recurrence remains a major cause of mortality in patients with rectal cancer. However, propionate metabolism-related genes (PMRGs) in rectal cancer remain insufficiently characterized. Therefore, this study aimed to identify prognostic biomarkers associated with lymph node metastasis and propionate metabolism and construct a risk‑prediction model for rectal cancer via bioinformatic analyses. METHODS: The Cancer Genome Atlas-Rectum Adenocarcinoma (TCGA-READ) and GSE87211 datasets, together with a curated PMRGs gene set, were used in this study. Pearson correlation analysis was performed to assess associations between overlapping genes (differentially expressed genes between READ and normal tissues, as well as between N0 and N1-N2 stages) and PMRGs, leading to the identification of candidate genes. Functional enrichment analyses were subsequently conducted to characterize the biological roles of these candidates. Prognostic biomarkers were identified using univariate Cox regression combined with least absolute shrinkage and selection operator (LASSO) regression, and a prognostic model was constructed accordingly. Independent prognostic validation was then performed. In addition, immune checkpoint profiling and immunotherapy response analyses were conducted across risk subgroups. Single-gene Gene Set Enrichment Analysis (GSEA) was applied to elucidate the pathways associated with the identified biomarkers. Finally, drug sensitivity analyses were performed. RESULTS: A total of 157 candidate genes were identified through the analytical pipeline. Functional enrichment analysis indicated that these genes were primarily involved in inflammatory response regulation and tumor necrosis factor (TNF) signaling pathways. Five prognostic biomarkers were subsequently identified and incorporated into a predictive model. External validation using the GSE87211 cohort confirmed the robustness of the model. Risk score and disease status were identified as independent prognostic factors. Six immune checkpoint molecules exhibited differential expression between risk groups. Correlation analyses revealed that the risk score was positively associated with most immune checkpoint genes. Single-gene GSEA demonstrated that the biomarkers were mainly enriched in ribosomal biogenesis and cell adhesion molecule-related pathways. Furthermore, 51 therapeutic agents exhibited significantly different half-maximal inhibitory concentration (IC50) values between risk subgroups. CONCLUSIONS: This study identified five biomarkers (CCL24, IGFBP3, ODC1, PYGM, and VKORC1) associated with lymph node metastasis and propionate metabolism pathways, providing a potential foundation for prognostic prediction in patients with rectal cancer.

Rectal cancer↗

PubMed2006

Systemic analysis of the differential gene expression profile in a colonic adenoma-normal SSH library.

BACKGROUND: The discovery of differentially expressed genes of colonic adenoma minus normal mucosa enables the understanding of early molecular events in colorectal carcinogenesis. In our previous study, we have developed an adenoma minus normal mucosa suppression subtractive hybridization (SSH) library and identified 109 differentially expressed clones. METHODS: An in-house EST pipeline and the Gene Ontology web-based tool () were used to analyze these clones. Realtime quantitative RT-PCR (Q-PCR) was applied to detect the expression of 14-3-3 zeta, REG4 and 6 ribosomal protein genes (RPS2, RPS12, RPS27A, RPL5, RPL7a and RPL10a) in 14 adenomas (8 with concurrent cancers) and 44 colorectal adenocarcinomas with paired normal mucosa. RESULTS: Sixty-two candidate genes were obtained from this library. Bioinformatics analysis indicated that both ribosomal protein genes and immune-related genes were enriched. REG4 was significantly upregulated in colorectal adenomas (medium fold: 1.676, p<0.05, Wilcoxon test) and 14-3-3 zeta in cancers (medium fold: 1.202, p<0.01, Wilcoxon test), as compared with those of paired normal mucosa. However, all ribosomal protein genes were not significantly overexpressed in colorectal adenomas or cancers. CONCLUSIONS: A differential gene expression profile in A-N SSH library may be helpful in understanding the molecular mechanism of colorectal cancer initiation and progression. REG4 and 14-3-3 zeta may be potential biomarkers for early colorectal cancer detection.

Adenoma↗