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European Journal of Medical Research Jan 2024The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received...
BACKGROUND
The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis.
METHODS
The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database.
RESULTS
PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer.
CONCLUSIONS
Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.
Topics: Humans; Female; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Biomarkers; Breast Neoplasms; Carcinoma, Renal Cell; Kidney Neoplasms; Prognosis; Tumor Microenvironment; Protein Tyrosine Phosphatase, Non-Receptor Type 3
PubMed: 38173048
DOI: 10.1186/s40001-023-01587-5 -
Frontiers in Veterinary Science 2023Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A...
Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A 7-year-old Mongrel dog was presented for a large oral and neck mass. Cytology and histopathology were suggestive of a round cell tumor that was suspected to be lymphoma. An immunohistochemical (IHC) stain panel showed positive for CD18, thus supporting the diagnosis of round cell tumor, but negative for T- and B-cell lymphomas, CD3, CD20, and PAX-5. Other markers including cytokeratin AE1/3 (for epithelial cell origin), CD31 (for endothelial cells), SOX10 (for melanoma), IBa-1 (for histiocytic sarcoma), and CD117 (for mast cell tumor) were all negative. MUM-1 (for plasma cell differentiation) was strongly positive and CD79a (B cell and plasma cells) was also scantly positive. Based on the histopathology and immunohistochemistry results in combination with the clinical presentation, a suspected diagnosis of PBL was made. As per available literature, this is perhaps the first highly suspected case of PBL in a dog.
PubMed: 36875999
DOI: 10.3389/fvets.2023.1100942 -
World Journal of Clinical Cases Oct 2021Two or multiple primary malignant neoplasms (MPMNs) rarely occur in the same patient. It has been reported that MPMNs are easily misdiagnosed as the recurrence or...
BACKGROUND
Two or multiple primary malignant neoplasms (MPMNs) rarely occur in the same patient. It has been reported that MPMNs are easily misdiagnosed as the recurrence or metastasis of malignancies in clinical practice, affecting the choice of treatment for the patients, thereby resulting in the delay of optimal diagnosis. Next generation sequencing (NGS) can be used to distinguish between multiple primary lung cancers and intrapulmonary metastasis, and may distinguish the origin of tumours in different sites of the body.
CASE SUMMARY
We report the case of 66-year-old woman who suffered from different malignant neoplasms in the rectum and esophageal and gastrointestinal tract. The first neoplasm rectal adenocarcinoma was diagnosed and removed in 2016. The second and third lesions were diagnosed with esophageal squamous-cell carcinoma (ESCC) and gastrointestinal stromal tumour (GIST), respectively, in 2019. Next-generation whole exome sequencing was performed on the tissue specimens of rectal carcinoma, esophageal cancer, GIST, and white blood cells to investigate the relationship between malignancies at different timeframe and determine whether the ESCC and GIST evolved from the rectal adenocarcinoma. Mutations including v-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog, adenomatosis polyposis coli, and mothers against decapentaplegic homolog 4 were detected in rectal adenocarcinoma sample, mast/stem cell growth factor receptor was detected in GIST tissue, and lysine methyltransferase 2D was detected in ESCC specimen. Overall, ESCC and GIST were not genetically evolved from rectal adenocarcinoma, and this patient did not have a trunk driven clone.
CONCLUSION
NGS is an effective tool to study clonal evolution of tumours and distinguish between MPMNs and intrapulmonary metastasis.
PubMed: 34754869
DOI: 10.12998/wjcc.v9.i28.8563 -
Canadian Journal of Veterinary Research... Oct 2020Immunohistochemistry has been used extensively to evaluate protein expression in clinical and research settings. However, immunohistochemistry is not always successful...
Immunohistochemistry has been used extensively to evaluate protein expression in clinical and research settings. However, immunohistochemistry is not always successful in veterinary medicine due to the lack of reliable antibody options, poor tissue preservation, labor-intensive staining, and antigen-retrieval optimization processes. RNAscope hybridization (ISH) is a powerful technology that uses a specific sequence probe to identify targeted mRNA. In this study, we demonstrate RNAscope ISH in 4 common canine malignancies, which are traditionally diagnosed by histopathology and immunohistochemistry. Probes were designed for commonly targeted mRNA markers of neoplastic tumors; these included c-kit in mast cell tumor, microphthalmia-associated transcription factor in malignant melanoma, ionized calcium-binding adapter molecule-1 in histiocytic sarcoma, and alkaline phosphatase in osteosarcoma. A strong staining signal was obtained by these 4 targets in each canine malignancy. These results support the use of RNAscope ISH for definitive diagnosis in canine malignancies.
Topics: Animals; Dog Diseases; Dogs; Immunohistochemistry; In Situ Hybridization; Neoplasms; RNA, Messenger
PubMed: 33012982
DOI: No ID Found -
Oncology Letters Sep 2019The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients,...
The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients, three patients were diagnosed with non-Hodgkin's lymphoma (NHL) and two patients with myeloid sarcoma (MS) of the uterine cervix. Biopsies of the uterine cervices demonstrated the involvement of lymphoid cells or myeloid blasts cells. Immunohistochemical staining demonstrated the expression of B-lymphoid and myeloid lineage markers. The associated lysozyme, myeloperoxidase and mast/stem cell growth factor receptor (CD117) markers were specific for the diagnosis of MS. The three patients with NHL survived, and one of the patients survived for 82 months with no evidence of disease; however, was eventually lost to follow-up. The two patients with MS succumbed to the cancer as a result of progressive disease and leukemia. Therefore, pathological examination may be important for the timely diagnosis and appropriate therapeutic regimen for primary hematological malignancy of the uterine cervix.
PubMed: 31516559
DOI: 10.3892/ol.2019.10652 -
Journal of Cutaneous Pathology Nov 2021We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred...
We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within 2 years, was reexcised after 4 years and did not recur >6 years after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67-staining from the onset. No KIT mutations were identified in the tumor and bone marrow. Serum tryptase levels and a bone marrow aspirate and trephine biopsy were normal. Although the histomorphology of the skin tumor was consistent with mast cell sarcoma, the clinical behavior without systemic progression argued against this diagnosis. The tumor was finally considered as atypical mastocytoma, borderline to mast cell sarcoma. Currently, the patient is in close follow-up and still in complete remission.
Topics: Adult; Diagnosis, Differential; Humans; Male; Mast-Cell Sarcoma; Mastocytoma, Skin
PubMed: 34152029
DOI: 10.1111/cup.14088 -
BMC Veterinary Research Aug 2022Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes...
BACKGROUND
Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosome concentrations in 528 dogs with various common malignancies and compare them to 134 healthy dogs.
RESULTS
The sensitivity of increased circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas, osteosarcoma and mast cell tumors.
CONCLUSIONS
A variety of tumor types may cause increased nucleosome concentrations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.
Topics: Animals; Bone Neoplasms; Dog Diseases; Dogs; Histones; Nucleosomes; Sarcoma
PubMed: 36045415
DOI: 10.1186/s12917-022-03429-8 -
Animals : An Open Access Journal From... Feb 2022Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human...
Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain plays a malignant role in cancer biology. However, currently, no publications have identified the role of legumain in the development of canine cancers. The present study first compared the expression patterns of legumain in paraffin-embedded canine tumor tissues, with those of normal tissues, by immunohistochemistry. A total of 100 canine tumor samples, including mast cell tumors, soft tissue sarcoma, hemangiosarcoma, lymphoma, mammary gland carcinoma, hepatoid gland tumor, squamous cell carcinoma, trichoblastoma, and melanoma were evaluated. Compared with the normal tissues, all tumor samples displayed high intensities of legumain expression. Mesenchymal-type tumors displayed immunoreactivity for legumain, with an average expression of 40.07% ± 1.70%, which was significantly lower than those of epithelial tumors and other types of tumors, which had median expressions of 49.12% ± 1.75% and 47.35% ± 2.71%, respectively ( < 0.05). These findings indicate that legumain has a high potential to be a candidate for distinguishing tumors from normal tissues. Although further studies on a larger number of cases are necessary to clarify the clinical application of legumain, the overexpression patterns of legumain in canine tumor tissues are reported, for the first time, in this study.
PubMed: 35203212
DOI: 10.3390/ani12040504 -
Animals : An Open Access Journal From... Apr 2022Since small mammals are gaining popularity as pets in Poland, the number of tumour samples submitted for histopathological examination is quite high. This study was a...
Since small mammals are gaining popularity as pets in Poland, the number of tumour samples submitted for histopathological examination is quite high. This study was a retrospective analysis of cutaneous and subcutaneous tumours in small pet mammals submitted for histopathology in 2014-2021. The analysis included 256 tumours sampled from 103 guinea pigs, 53 rats, 43 pet rabbits, 21 ferrets, 17 hamsters, 8 degus, 5 African pygmy hedgehogs, 3 Mongolian gerbils and 3 chinchillas. Tumours were diagnosed based on routine histopathology, with additional immunohistochemistry when necessary. The results of this study revealed that the vast majority of cutaneous tumours in guinea pigs were benign, with a predominance of lipoma. Adnexal tumours constituted a significant percentage of cutaneous tumours in guinea pigs (24.3%, with the most common being trichofolliculoma), pet rabbits (46.5%, with the most common being trichoblastoma), ferrets (33.3%, mostly derived from sebaceous glands), hamsters (52.9%, with the most common being trichoepithelioma) and gerbils (66.7%, scent gland epithelioma). Soft tissue sarcomas were a predominant group of tumours in rats (52.8%, with the most common being fibrosarcoma), African pygmy hedgehogs (100%), degus (87.5%) and chinchillas (66.7%). Melanocytic tumours were only sporadically seen in small mammal pets. Mast cell tumours were diagnosed only in ferrets, while epitheliotropic T-cell lymphoma was diagnosed only in a hamster and a degu. In summary, malignant tumours constitute a significant percentage of cutaneous tumours in many species of small mammal pets. Therefore, each cutaneous tumour should be sampled for further cytologic or histopathologic diagnosis.
PubMed: 35454212
DOI: 10.3390/ani12080965 -
Medicine Jun 2024To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and...
To explore the expression and prognostic value of UHRF1 gene in soft tissue sarcoma (STS) and its related molecular mechanism. The expression data and clinicopathological parameters of STS were downloaded from the Cancer Genome Atlas (TCGA). The expression level of UHRF1 in STS and adjacent tissues and its relationship with clinicopathological characteristics were analyzed. The expression level of UHRF1 in STS tissues was significantly higher than that in paracancerous tissues (P < .001), and the overall survival (OS) time of patients with high UHRF1 expression was significantly shorter than that of patients with low UHRF1 expression (P = .002). The expression of UHRF1 was correlated with tumor necrosis, histological type and metastasis, and the differences were statistically significant (P = .013; P = .001; P = .002). The area ratio under receiver operating characteristic (ROC) curve between STS tissue and adjacent tissue of UHRF1 expression was 0.994. Number of tumors (HR = 0.416, 95%CI = 0.260-0.666, P < .001), depth of tumor (HR = 2.888, 95%CI = 0.910-9.168, P = .033), metastasis (HR = 2.888, 95% CI = 1.762-4.732, P < .001), residual tumor (HR = 2.637, 95% CI = 1.721-4.038, P < .001) and UHRF1 expression (HR = 1.342, 95% CI = 1.105-1.630, P = .003) were significantly associated with OS, and high expression of UHRF1 (HR = 1.387, 95%CI = 1.008-1.907, P = .044) was an independent risk factor for the prognosis of STS patients. The results of the nomogram exhibited that UHRF1 expression level had a significant effect on the total score value. GSEA enrichment analysis suggested that UHRF1 was involved in 14 signaling pathways regulating mRNA spliceosome, cell cycle, P53 signaling pathway were identified. Single sample gene set enrichment analysis (ssGSEA) exhibited that the expression of UHRF1 in STS was positively correlated with the level of Th2 cell infiltration, and negatively correlated with plasmacytoid dendritic cells (pDC), natural killer cells (NK), Eosinophils, Mast cells, etc. UHRF1 expression is involved in the immune microenvironment of HCC and affects the occurrence and development of HCC. UHRF1 is highly expressed in STS tissues. It is involved in the regulation of multiple tumor-related signaling pathways and immune cell microenvironment, suggesting that UHRF1 may be a potential molecular marker for prognosis prediction and targeted therapy of STS patients.
Topics: Humans; CCAAT-Enhancer-Binding Proteins; Ubiquitin-Protein Ligases; Sarcoma; Female; Prognosis; Male; Middle Aged; Biomarkers, Tumor; Adult; ROC Curve; Aged; Clinical Relevance
PubMed: 38847665
DOI: 10.1097/MD.0000000000038393