Phylostratigraphic analysis of tumor and developmental transcriptomes reveals relationship between oncogenesis, phylogenesis and ontogenesis

Prognostic implication of aberrant promoter hypermethylation of CpG islands in adenocarcinoma of the lung

Impacts of transmembrane serine protease 4 expression on susceptibility to severe acute respiratory syndrome coronavirus 2.

Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance

Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues

BackgroundThe FAM83 family plays a key role in tumorigenesis and cancer progression. However, the role of the FAM83 family in the development of breast tumors is unclear to date. This report explores the expression, prognostic significance, and function of the FAM83 family members in breast cancer using public databases.MethodsUALCAN database was used to explore the expression of FAM83 family members in breast cancer. Furthermore, we validated the expression of FAM83 family members in twenty pairs of breast cancer and normal tissues by RT-PCR. Kaplan–Meier plotter database was used to explore the prognostic significance of FAM83 family members in breast cancer. GeneMANIA and DAVID databases were used for functional and pathway enrichment analysis of genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G. MEXPRESS and UALCAN databases were used to analyze the level of DNA promoter methylation of FAM83A, FAM83D, FAM83F, and FAM83G in breast cancer. TIMER database was utilized to explore the relationships between immune cell infiltration and FAM83A, FAM83D, FAM83F, and FAM83G expression.ResultsAmong FAM83 family members, FAM83A, FAM83D, FAM83F, and FAM83G were higher expressed in breast cancer than in normal tissues. We also validated the significant high expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in breast cancer than in normal samples. Their increased expression has an adverse prognostic effect on breast cancer patients. These genes co-expressed with FAM83A, FAM83D, FAM83F, and FAM83G might take part in cell proliferation, G2/M transition of the mitotic cell cycle, regulation of apoptosis process and other cancer-related biological processes. In addition, they were mainly enriched in the Hippo signaling pathway, Hedgehog signaling pathway, PI3K/AKT signaling pathway, and other cancer-related pathways. We also found that promoter DNA methylation might regulate the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA in most CpG islands. At last, we found the expression of FAM83A, FAM83D, FAM83F, and FAM83G mRNA was significantly related to immune cell infiltration.ConclusionsFAM83A, FAM83D, FAM83F, and FAM83G were highly expressed in breast cancer tissues and had an adverse effect on the survival outcomes of breast cancer patients. Also, they were involved in breast cancer-related signal pathways. Therefore, they might serve as potential therapeutic targets for breast cancer clinical treatment.

Transforming growth factor α,β(TGF α,β) acted as positive and negative growth regulators respectively play an important role in the development and progression of colorectal carcinoma. In this study, the dot, Northern and Southern blot analysis were used to explore the expressions and changes of TGF-α,β genes of colorectal cancerous, paracancerous and normal mucosal tissues in 12 cases. The order of the expressions of TGF-a mRNA from high to low is cancerous, paracancerous and normal tissues in turn. In one case, the expression of TGF-α mRNA was much higher in paracancerous tissues, even than that in the cancerous tissues. The order of expressions of TGF-β mRNA from high to low was contrary to that of the TGF-α mRNA. That is from normal, paracancerous and cancerous tissues in turn. In two cases of patients, the expression of TGF-β mRNA were higher in paracancerous tissues than that in normal tissues. We also found that the amplification of TGF-α gene may be lead to the high expression of TGF-β mRNA were not known. These results indicate that the higher expression of TGF-α and the lower expression of TGF-β in cancerous tissues and the higher expressions of TGF-α, β in paracancerous tissues of some cases may be correlated with the development and progression of the colorectal carcinoma by autocrine or paracrine growth regulation.

Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases α and π, glutathione and aldehyde dehydrogenase

1132 Background: Routine intra-operative distinction between normal breast tissue and tumor is currently not possible in breast conserving surgery (BCS). This limitation affects the success of surgery, resulting in up to 40% requiring more than one operative procedure. Desorption electrospray ionization mass spectrometry (DESI MS) has been successfully used to discriminate between normal and cancerous human tissues from anatomical sites such as the liver and brain. The aim of this proof of concept study was to determine the feasibility of using DESI MS imaging for tissue identification and differentiation of breast cancer versus normal tissue. Methods: DESI MS imaging was carried out on 14 human invasive breast cancer samples. Breast cancer and adjacent normal paired human tissue sections (margin of tumor, 2cm and 5 cm from tumor) from 14 patients undergoing mastectomy were flash frozen in liquid nitrogen, sectioned, and thaw mounted to glass slides. All samples were imaged using DESI MS at 200 μm imaging resolution. DESI MS images were overlaid and compared with hematoxylin and eosin (H&E) images of the same sections. Results: Discrimination between cancer and adjacent normal tissue was achieved on the basis of the spatial distribution and varying intensities of particular fatty acids and lipid species. Several fatty acids such as oleic acid (m/z 281) and arachidonic acid (m/z 303) displayed much greater signal intensities in the cancer specimen compared to low or undetectable intensities in normal tissue. The cancer margins delineated by the DESI MS images of these molecules were consistent with H and E images of the tumor edge. Cancerous tissue was distinguished from normal tissue based on the qualitative assessment of molecular signatures and the distinction was in agreement with expert histopathology evaluation in 85% of samples. Conclusions: Our findings offer proof of concept that examination and classification of breast normal and cancer tissue by mass spectrometry imaging is highly accurate. The results are encouraging for development of a MS-based method that could be utilized intra-operatively for rapid detection of residual cancer tissue in the lumpectomy bed in BCS.

Transient state, excitation spectra, and time- resolved spectroscopic dynamics from normal and cancerous human breast and lung tissues have been studied and are presented. The spectral profiles obtained from samples excited with the second and third harmonic of a picosecond pulse Nd:glass laser were different for normal and cancerous tissues. The main peaks at ~450 nm were shifted, while the subsidiary peaks of normal tissues smoothed out in the cancerous tissues with less structure. The excitation spectra for the three different emission wavelengths at 520, 550, and 600 nm corresponding to the three peaks in the normal tissue fluorescence spectra were measured. The overall excitation spectra showed broad UV and visible bands with differences between the cancerous and normal tissues. The dynamic profiles of the fluorescence spectra were measured using photoexcitation by 350- and 530 nm light from a picosecond pulse Nd:glass laser and a streak camera detection system. The kinetic profiles showed faster decay times for the cancerous tissues compared with normal tissues. The spectroscopic differences were attributed to changes in flavins, porphyrins, and the surrounding media.

Objective To investigate the expression level of C-type lectin domain family 4 member G (CLEC4G) in liver disease tissues and its correlation with the clinicopathological characteristics of hepatocellular carcinoma (HCC) patients. Methods The cancer tissue and the corresponding adjacent tissues (at least 2 cm from the edge of the cancer tissue), cut in surgeries from January to December in 2019, of 40 HCC patients in Zhuzhou Central Hospital, as well as 10 normal liver tissue samples (seen as far away as possible from the edge of the cancer tissue with naked eyes) and 10 liver cirrhosis samples were analyzed retrospectively. The tumor genome atlas (TCGA) database was used to screen the HCC transcriptome data sets, and bioinformatics methods were used to make expression heat maps and box maps which can help analyze the difference of CLEC4G in cancer and adjacent tissues. The mRNA expression level of CLEC4G was detected by conducting real-time fluorescence quantitative PCR (qRT-PCR), and the protein expression level of CLEC4G was detected by immunohistochemistry (IHC). The measurement data were expressed as mean±standard deviation (Mean±SD). Group t test was used for inter-group comparison. The counting information was expressed as a percentage (%). The χ2 test was adopted to analyze the correlation between CLEC4G expression level and the clinicopathological features of patients. Results The expression level of CLEC4G in cancer tissues was significantly decreased in heat map compared with that in adjacent tissues. In the box figure, the relative expression of CLEC4G mRNA in the cancer tissues was (82.5±18.9) and (3 354.4±296.2) in paracancer tissues, with statistically significant difference (P<0.001). Respectively, qRT-PCR and IHC showed that mRNA of CLEC4G were abundant in normal liver tissues (3 301.3±286.4), while they were very little in liver cancer tissues (63.6±32.9), significantly decreasing in liver cirrhosis (1 742.6±208.7) and paracancer tissues (1 553.2±249.9), with statistically significant difference (P<0.001). Moreover, low CLEC4G expression level was associated with tumor vascular metastasis in HCC patients. Conclusions CLEC4G is highly expressed in normal liver tissue, but with the progression of malignant liver disease, it is significantly decreased with little expression in HCC tissue. It can be expected to be a good marker for the pathological diagnosis of HCC. Key words: Carcinoma, hepatocellular; Liver cirrhosis; Neoplasms, vascular tissue; Liver tissue

BackgroundIt is well known that pepsinogen (PGs), as an important precursor of pepsin performing digestive function, has a good correlation with the occurrence and development of gastric cancer and it is also known that ectopic PGs expression is related to the prognosis of some cancers. However, the panoramic picture of pepsinogen gene family in human cancer is not clear. This study focused on elucidating the expression profile, activated pathway, immune cells infiltration, mutation, and copy number variation of PGs and their potential role in human cancer.MethodBased on the next generation sequence data from TCGA, Oncomine, and CCLE, the molecular changes and clinical correlation of PGs in 33 tumor types were analyzed systematically by R language, including the expression, mutation, and copy number variation of PGs and their correlation with cancer‐related signal transduction pathway, immune cell infiltration, and prognostic potential in different cancers.ResultsPGs expression profiles appear different in 33 tumors. The transcriptional expression of PGs was detected in 16 of all 33 tumors. PGC was highly expressed in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, uterine corpus endometrial carcinoma, bladder urothelial carcinoma and breast cancer, while decreased in stomach adenocarcinoma, kidney renal clear cell carcinoma, prostate adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. PGA3, PGA4, and PGA5 were expressed in most normal tissues, but decreased in cancer tissues. PGs expression was significantly related to the activation or inhibition of many signal transduction pathways, in which PGC and PGA5 are more likely to be associated with cancer‐related pathways. PGC participated in 33 regulatory network pathways in pan‐cancer, mainly distributed in stomach adenocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma, respectively. PGC and PGA3 expression were significantly correlated with immune cell infiltration. The results of survival analysis showed that different PGs expression play significantly different prognostic roles in different cancers. PGC was correlated with poor survival in brain lower grade glioma, skin cutaneous melanoma, and higher survival in kidney renal clear cell carcinoma, acute myeloid leukemia, mesothelioma, and uveal melanoma. PGA4 was only associated with higher survival in kidney renal clear cell carcinoma. Genetic variation analysis showed that PGC gene often mutated in uterine corpus endometrial carcinoma and stomach adenocarcinoma had extensive copy number amplification in various tumor types. PGC expression was upregulated with the increase of copy number in cholangiocarcinoma, esophageal carcinoma, and kidney renal papillary cell carcinoma, while in stomach adenocarcinoma, PGC was upregulated regardless of whether the copy number was increased or decreased.ConclusionsPGs was expressed unevenly in a variety of cancer tissues and was related to many carcinogenic pathways and involved in the immune regulation. PGC participated in 33 regulatory pathways in human cancer. Different PGs expression play significantly different prognostic roles in different cancers. The variation of copy number of PGC gene could affect the PGC expression. These findings suggested that PGs, especially PGC have characteristic of broad‐spectrum expression in multiple cancers rather than being confined to the gastric mucosa, which may made PGs be useful biomarkers for prediction/diagnosis/prognosis and effective targets for treatment in human cancer.

Analysis of gene expression profiles of gastric normal and cancer tissues by SAGE

Introduction/BackgroundOwing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma (SCC-MT) remain unclear. This study aims to elucidate the molecular background of...

Differential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated by Cis Noncoding Mutations.

HOX genes are known not only as master genes that control the morphogenesis, but also as regulator genes that maintain tissue or organ specificity in the adult body. We hypothesized that dysregulated expression of HOX genes was associated with tumor development and malignant progression such as invasion and metastasis. In this study, we analyzed the expression patterns of 39 HOX genes in human invasive ductal breast cancer tissues and normal tissues by the real-time RT-PCR method. We found 11 HOX genes (HOXA1, A2, A3, A5, A9, C11, D3, D4, D8, D9 and D10) expression levels of which were significantly different between cancerous and normal tissues. All 10 genes except HOXC11 were expressed at lower levels in cancerous tissues than normal tissues. Comparing expression levels of each HOX gene among the different types of cancer tissues, the expression level of HOXB7 was lower in lymph node metastasis-positive cancer tissues than negative cancer tissues; those of HOXD12 and D13 were higher in progesterone receptor-positive cancer tissues than negative cancer tissues; and the expression level of HOXC5 was lower in cancerous tissues with mutated-type p53 than in normal and cancerous tissues with wild-type p53. These results suggest that the aberrant expression of HOX genes is related to the development of breast cancer and malignant behavior of cancer cells.