scholarly journals Gene Expression Profiling for Differential Diagnosis of Liver Metastases: A Multicenter, Retrospective Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Qifeng Wang ◽  
Fen Li ◽  
Qingming Jiang ◽  
Yifeng Sun ◽  
Qiong Liao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Metastases ◽  
Liver Tumor ◽  
Primary Tumor ◽  
Liver Tumors ◽  
Gene Signature ◽  
Difficult Problem ◽  
Primary Liver Tumor ◽  
Gene Expression Assay ◽  
Tumor Types

BackgroundLiver metastases (LM) are the most common tumors encountered in the liver and continue to be a significant cause of morbidity and mortality. Identification of the primary tumor of any LM is crucial for the implementation of effective and tailored treatment approaches, which still represents a difficult problem in clinical practice.MethodsThe resection or biopsy specimens and associated clinicopathologic data were archived from seven independent centers between January 2017 and December 2020. The primary tumor sites of liver tumors were verified through evaluation of available medical records, pathological and imaging information. The performance of a 90-gene expression assay for the determination of the site of tumor origin was assessed.ResultA total of 130 LM covering 15 tumor types and 16 primary liver tumor specimens that met all quality control criteria were analyzed by the 90-gene expression assay. Among 130 LM cases, tumors were most frequently located in the colorectum, ovary and breast. Overall, the analysis of the 90-gene signature showed 93.1% and 100% agreement rates with the reference diagnosis in LM and primary liver tumor, respectively. For the common primary tumor types, the concordance rate was 100%, 95.7%, 100%, 93.8%, 87.5% for classifying the LM from the ovary, colorectum, breast, neuroendocrine, and pancreas, respectively.ConclusionThe overall accuracy of 93.8% demonstrates encouraging performance of the 90-gene expression assay in identifying the primary sites of liver tumors. Future incorporation of the 90-gene expression assay in clinical diagnosis will aid oncologists in applying precise treatments, leading to improved care and outcomes for LM patients.

scholarly journals Protein expression of prognostic genes in primary melanoma and benign nevi

2021 ◽  
Author(s):  
T. Gambichler ◽  
J. Elfering ◽  
T. Meyer ◽  
S. Bruckmüller ◽  
E. Stockfleth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Primary Tumor ◽  
Primary Melanoma ◽  
Superficial Spreading ◽  
Acral Lentiginous Melanoma ◽  
Expression Levels ◽  
Gene Expression Assay ◽  
Prognostic Gene ◽  
Associated Functions

Abstract Purpose To evaluate the protein expression characteristics of genes employed in a recently introduced prognostic gene expression assay for patients with cutaneous melanoma (CM). Methods We studied 37 patients with CM and 10 with benign (melanocytic) nevi (BN). Immunohistochemistry of primary tumor tissue was performed for eight proteins: COL6A6, DCD, GBP4, KLHL41, KRT9, PIP, SCGB1D2, SCGB2A2. Results The protein expression of most markers investigated was relatively low (e.g., DCD, KRT9, SCGB1D2) and predominantly cytoplasmatic in melanocytes and keratinocytes. COL6A6, GBP4, and KLHL41 expression was significantly enhanced in CM when compared to BN. DCD protein expression was significantly correlated with COL6A6, GBP4, and KLHL41. GBP4 was positively correlated with KLHL41 and inversely correlated with SCGB2B2. The latter was also inversely correlated with serum S100B levels at time of initial diagnosis. The presence of SCGB1D2 expression was significantly associated with ulceration of the primary tumor. KRT9 protein expression was significantly more likely found in acral lentiginous melanoma. The presence of DCD expression was less likely associated with superficial spreading melanoma subtype but significantly associated with non-progressive disease. The absence of SCGB2A2 expression was significantly more often observed in patients who did not progress to stage III or IV. Conclusions The expression levels observed were relatively low but differed in part with those found in BN. Even though we detected some significant correlations between the protein expression levels and clinical parameters (e.g., CM subtype, course of disease), there was no major concordance with the protective or risk-associated functions of the corresponding genes included in a recently introduced prognostic gene expression assay.

Acceleration of primary liver tumor growth rate in embolized hepatic lobe after portal vein embolization

2007 ◽  
Vol 48 (7) ◽  
pp. 721-727 ◽  
Author(s):  
S. Hayashi ◽  
Y. Baba ◽  
K. Ueno ◽  
M. Nakajo ◽  
F. Kubo ◽  
...  
Keyword(s):  
Growth Rate ◽  
Portal Vein ◽  
Tumor Growth ◽  
Liver Tumor ◽  
Portal Vein Embolization ◽  
Liver Tumors ◽  
Liver Parenchyma ◽  
Tumor Growth Rate ◽  
Primary Liver Tumor ◽  
Day Range

Background: Portal vein embolization (PVE) is now widely accepted as a useful preoperative procedure in selected patients undergoing extended hepatectomy. However, the effect of PVE on the growth of liver tumors has not been fully elucidated. Purpose: To retrospectively evaluate the effects of PVE on the growth of liver tumors in the embolized lobes. Material and Methods: Eight patients with a primary liver tumor, six hepatocellular carcinomas (HCC) and two cholangiocellular carcinomas (CCC), were studied. The growth rates of the tumors in the embolized lobes and non-embolized liver parenchyma were calculated using the computed tomography (CT) volume values at the time of tumor identification, and before and after PVE. Result: The median tumor growth rate was 0.59 cm3/day (range 0.22–6.01 cm3/day) before PVE and 2.37 cm3/day (range 0.29–13.97 cm3/day) after PVE ( P = 0.018). The tumor growth acceleration ratios ranged from 1.50 to 7.46 (median 2.65) in the six HCCs, and were 1.00 and 1.32 in the two CCCs. There was no apparent correlation between the tumor growth rate after PVE and the growth rate of non-embolized liver parenchyma (median 6.00 cm3/day, range 1.24–11.0 cm3/day). Conclusion: Liver tumor growth in an embolized lobe accelerates after PVE, in patients with HCC.

scholarly journals Gene Expression Profiling For Diagnosis of Multiple Primary Malignant Tumors

2020 ◽  
Author(s):  
Yu Zheng ◽  
Yifeng Sun ◽  
Yue Kuai ◽  
Guoxiang Fu ◽  
Huimin An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Malignant Tumors ◽  
Clinical Specimen ◽  
Tumor Type ◽  
Significant Treatment ◽  
Gene Expression Assay ◽  
Multiple Primary ◽  
Tumor Types

Abstract Background: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and the increased aging of the population. For patients with a prior cancer history, distinguishing tumor recurrence or metastasis from a second malignant tumor has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. Methods: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Twenty-four MPMT patients from Sir Run Run Shaw Hospital, college of medicine, Zhejiang University were enrolled in this study. A total of 51 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. Results: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its reference diagnosis with an overall accuracy of 94.1% (48 of 51, 95% confidence interval: 0.83-0.98). Additionally, the hierarchical clustering of 90-gene expression profiling in 51 specimens revealed MPMT samples were grouped together depending on tumor types or system types rather than individual MPMT patients. Conclusions: Therefore, the 90-gene expression assay provides flexibility and accuracy in identifying the tissue origin of MPMTs, especially in squamous cell carcinoma. Future incorporation of the 90-gene expression assay in the pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

scholarly journals Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 158
Author(s):  
Valentina Condelli ◽  
Giovanni Calice ◽  
Alessandra Cassano ◽  
Michele Basso ◽  
Maria Grazia Rodriquenz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Poor Prognosis ◽  
Cpg Island ◽  
Colon Adenocarcinoma ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cpg Island Methylator Phenotype ◽  
Prognostic Information ◽  
Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

scholarly journals A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Checkpoints ◽  
The Novel ◽  
The Central Nervous System ◽  
Checkpoint Genes

Abstract Background Glioma is the most common and fatal type of nerve neoplasm in the central nervous system. Several biomarkers have been considered for prognosis prediction, which is not accurate enough. We aimed to carry out a gene signature related to the expression of immune checkpoints which was enough for its performance in prediction. Methods Gene expression of immune checkpoints in TGGA database was filtrated. The 5 selected genes underwent verification by COX and Lasso-COX regression. Next, the selected genes were included to build a novel signature for further analysis. Results Patients were sub-grouped into high and low risk according to the novel signature. Immune response, clinicopathologic characters, and survival showed significant differences between those 2 groups. Terms including “naive,” “effector,” and “IL-4” were screened out by GSEA. The results showed strong relevance between the signature and immune response. Conclusions We constructed a gene signature with 5 immune checkpoints. The signature predicted survival effectively. The novel signature performed more functional than previous biomarkers.

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