Artificial Intelligence for Replacing Manual Protein Abundance Assessment in Cirrhotic and Liver Cancer Tissue Samples

Liver cancer is a common malignant tumor worldwide, which is a serious threat to the health of people. We try to investigate some mutations and clinical indicators as candidate markers for the development of liver cancer through targeted region capture technology combined with next-generation sequencing. We collected peripheral blood and liver cancer tissue samples from 32 liver patients concurrently. The SeqCap EZ Prime Choice Probe was used to perform the targeted enrichment; this probe captures 1,000 known cancer-associated genes. We calculated the tumor mutation burden (TMB) for each patient. The high-frequency mutations and these relative genes were identified. Eventually, survival analysis was performed based on the mutations and clinical indicators. In 32 liver patients, a total of 29 high-frequency mutations were investigated. They were located in 25 genes, which were enriched in 9 cellular components (CCs), 6 molecular functions (MFs), and 21 biological processes (BPs). Among them, EZH2 c.1544A>G and CCND1 c.839A>T had the highest mutation frequency (5/32). In the protein–protein interaction (PPI) network, EZH2-DNMT3A, NOTCH1-CCND1, and ABL1-CCND1 were the top three pairs. The survival analysis showed that there were significant differences in progression-free survival (PFS) and overall survival (OS) between the Karnofsky performance score (KPS) groups. The PFS and OS in the TMB high group were higher than those in the TMB low group. OS and tumor stage had a remarkable relationship. In conclusion, EZH2 c.1544A>G and CCND1 c.839A>T might be potential biomarkers of liver cancer. TMB might be used as a prognosis and survival indicator of liver cancer.

Download Full-text

Role of microRNA miR-34a in liver cancer stem cells

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i2.24975 ◽

2016 ◽

Vol 11 (2) ◽

pp. 333

Author(s):

Lu-Lu Gong ◽

Shu-Li Yang ◽

Guo-Feng Zhang ◽

Jia-Chengi Wu ◽

Rui-Xin Lin

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Liver Cancer ◽

Liver Tissue ◽

Normal Liver ◽

Cancer Tissue ◽

Tissue Samples ◽

Liver Cancer Stem Cells ◽

Important Target

The present study focuses on the role of microRNA miR-34a in liver cancer stem cells. Liver tissue samples were collected from the control and liver cancer patients. Immunohistochemistry experiment with CD90 antibodies suggests that the liver cancer stem cells were present in the liver cancer tissue samples. Interestingly, flow cytometry analysis followed by qRT-PCR confirmed that the CD90+ cells also called as liver cancer stem cells shows expression of miR-34a at the levels of 30-80%, when compared with that of normal liver tissue samples. The present study concludes that the liver cancer stem cells shows high expression of miR-34a, which is the important target unique to liver cancer stem cells in order to design liver cancer stem cells-specific therapies.

Download Full-text

A PILOT STUDY OF HER-2/NEU GENE AMPLIFICATION ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN GASTRIC CANCER

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2014.3.2 ◽

2014 ◽

pp. 15-20

Author(s):

Van Huy Tran ◽

Thi Minh Thi Ha ◽

Trung Nghia Van ◽

Viet Nhan Nguyen ◽

Phan Tuong Quynh Le ◽

...

Keyword(s):

Gastric Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Cancer Patients ◽

Gene Amplification ◽

Cancer Tissue ◽

Tissue Samples ◽

Her 2 ◽

Gastric Cancer Patients

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.

Download Full-text

Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13112560 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2560

Author(s):

Luis G. Guijarro ◽

Patricia Sanmartin-Salinas ◽

Eva Pérez-Cuevas ◽

M. Val Toledo-Lobo ◽

Jorge Monserrat ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Hepg2 Cells ◽

Cellular Polarity ◽

Ki 67 ◽

Tissue Samples ◽

Vitro Analysis ◽

Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

Download Full-text

EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Cancers ◽

10.3390/cancers13061410 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1410

Author(s):

Anna Buchholz ◽

Aurelia Vattai ◽

Sophie Fürst ◽

Theresa Vilsmaier ◽

Christina Kuhn ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Vulvar Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Common Finding ◽

Cancer Tissue ◽

Vulvar Carcinoma ◽

Tissue Samples

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

Download Full-text

Nanoparticles in enhancing microwave imaging and microwave Hyperthermia effect for liver cancer treatment

REVIEWS ON ADVANCED MATERIALS SCIENCE ◽

10.1515/rams-2021-0014 ◽

2021 ◽

Vol 60 (1) ◽

pp. 223-236

Author(s):

Walaa Maamoun ◽

Mohamed I. Badawi ◽

Ayman A Aly ◽

Y. Khedr

Keyword(s):

Silver Nanoparticles ◽

Liver Cancer ◽

Cancer Treatment ◽

Electromagnetic Waves ◽

Microwave Imaging ◽

Healthy Tissue ◽

Cancer Tissue ◽

Hyperthermia Treatment ◽

Hyperthermia Therapy ◽

Surrounding Healthy Tissue

Abstract Hyperthermia therapy is a promising therapy for liver cancer treatment that utilizes external electromagnetic waves to heat the tumor zone to preferentially kill or minimize cancer cells. Nevertheless, it’s a challenge to realize localized heating of the cancer tissue without harming the surrounding healthy tissue. This research proposes to utilize nanoparticles as microwave absorbers to enhance microwave imaging and achieve localized hyperthermia therapy. A realistic 3D abdomen model has been segmented using 3D Slicer segmentation software, and then the obtained segmented CAD model exported to Computer Simulation Technology (CST STUDIO) for applying the Finite Element Modeling (FEM). Next investigating both imaging and treatment capability. Finally, the specific absorption rate (SAR) and temperature distribution were computed without nanoparticles and with different types of nanoparticles such as gold (GNPs) and silver nanoparticles at frequency 915 MHz. By comparing the achived results, it was seen that Silver nanoparticles can make a great enhancement in raising the temperature. However, this result was unsatisfactory but, after adding gold nanoparticles the temperature exceed 42°C, at frequency 915 MHz which is achieving the hyperthermia treatment without harming the nearby healthy tissue, GNPs also can achieve a great enhancement in SAR result

Download Full-text

Strategy for SRM-based Verification of Biomarker Candidates Discovered by iTRAQ Method in Limited Breast Cancer Tissue Samples

Journal of Proteome Research ◽

10.1021/pr300322q ◽

2012 ◽

Vol 11 (8) ◽

pp. 4201-4210 ◽

Cited By ~ 52

Author(s):

Satoshi Muraoka ◽

Hideaki Kume ◽

Shio Watanabe ◽

Jun Adachi ◽

Masayoshi Kuwano ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Tissue Samples

Download Full-text

RNA Sequencing in Comparison to Immunohistochemistry for Measuring Cancer Biomarkers in Breast Cancer and Lung Cancer Specimens

Biomedicines ◽

10.3390/biomedicines8050114 ◽

2020 ◽

Vol 8 (5) ◽

pp. 114

Author(s):

Maxim Sorokin ◽

Kirill Ignatev ◽

Elena Poddubskaya ◽

Uliana Vladimirova ◽

Nurshat Gaifullin ◽

...

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Rna Sequencing ◽

Expression Profiles ◽

Correlation Study ◽

Cancer Tissue ◽

Transcriptional Level ◽

Tissue Samples ◽

Protein Levels ◽

Formalin Fixed Paraffin Embedded

RNA sequencing is considered the gold standard for high-throughput profiling of gene expression at the transcriptional level. Its increasing importance in cancer research and molecular diagnostics is reflected in the growing number of its mentions in scientific literature and clinical trial reports. However, the use of different reagents and protocols for RNA sequencing often produces incompatible results. Recently, we published the Oncobox Atlas of RNA sequencing profiles for normal human tissues obtained from healthy donors killed in road accidents. This is a database of molecular profiles obtained using uniform protocol and reagents settings that can be broadly used in biomedicine for data normalization in pathology, including cancer. Here, we publish new original 39 breast cancer (BC) and 19 lung cancer (LC) RNA sequencing profiles obtained for formalin-fixed paraffin-embedded (FFPE) tissue samples, fully compatible with the Oncobox Atlas. We performed the first correlation study of RNA sequencing and immunohistochemistry-measured expression profiles for the clinically actionable biomarker genes in FFPE cancer tissue samples. We demonstrated high (Spearman’s rho 0.65–0.798) and statistically significant (p < 0.00004) correlations between the RNA sequencing (Oncobox protocol) and immunohistochemical measurements for HER2/ERBB2, ER/ESR1 and PGR genes in BC, and for PDL1 gene in LC; AUC: 0.963 for HER2, 0.921 for ESR1, 0.912 for PGR, and 0.922 for PDL1. To our knowledge, this is the first validation that total RNA sequencing of archived FFPE materials provides a reliable estimation of marker protein levels. These results show that in the future, RNA sequencing can complement immunohistochemistry for reliable measurements of the expression biomarkers in FFPE cancer samples.

Download Full-text

Diagonistic Value of ARFI in Breast Lesions

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i50b33421 ◽

2021 ◽

pp. 24-30

Author(s):

J. Jayapriya ◽

S. Arul Murugan

Keyword(s):

Breast Cancer ◽

Acoustic Radiation ◽

Radiation Force ◽

Acoustic Radiation Force Impulse ◽

Stiffness Index ◽

Cancer Tissue ◽

Cancer Type ◽

Tissue Samples ◽

Biopsy Confirmation ◽

Index Value

Breast cancer became the most prominent cancer type in women worldwide. Its prevalence increased in recent years due to changes in life style and relapse among the patients seemed to be higher. Acoustic radiation force impulse (ARFI) imaging in based on the principle of the ultrasonic elasticity and the elestography accurately predict and measure the changes in breast cancer tissue compared to the normal tissue. It is a technical alternative to the palpation and able to measure lesser than 10 mm size. In contrast to biopsy, where the reduced deformability would occur and lead to biopsy failing. In fibroadenoma, due to its complications, many false positives could be detected and the ARFI elastography serve as an effective alternative method for breast cancer confirmation. The tissue stiffness index value is used to differentiate the benign and malignant tissue samples. ARFI further, use B- mode elasticity and help in recommending the biopsy confirmation.

Download Full-text

Cytogenetic differences in blood and cancer tissue samples of the same patient group

Cancer Research and Cellular Therapeutics ◽

10.31579/2640-1053/070 ◽

2020 ◽

Vol 4 (1) ◽

pp. 01-03

Author(s):

Osman Demirhan ◽

Deniz Taştemir Korkmaz ◽

Nesrin Çetinel

Keyword(s):

Malignant Disease ◽

Chromosomal Abnormalities ◽

Cancer Tissue ◽

Tissue Samples ◽

Genetic Changes ◽

Tumor Tissues ◽

Cancer Tissues ◽

Gene Expression Alterations ◽

Breast Tissues ◽

Improved Methods

Breast cancer (BC) is the most prevalent malignant disease in females worldwide. Genomic instability in tumor tissue has been associated with tumor progression. These genetic changes may take a variety of forms, including numerical and structural chromosomal abnormalities (CAs), epigenetic changes, and gene expression alterations. Many tumor tissues are made up of genetically different cell populations, and the study of the causes and consequences of this heterogeneity play a central role in cancer research. In this study, CAs in blood and cancer tissues of patients with sporadic BC were examined. Our findings shows that the increase in numerical sex aneuploidy in BC tissues is significantly higher than in blood tissue. These aneuploidy increases in cancer tissues seem to be compatible with the development and increase of cancer, and can play a role in the pathogenesis of cancers. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. These findings should clarify our understanding of breast carcinogenesis in breast tissues and promote development of improved methods for risk assessment and BC prevention in women.

Download Full-text