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Computational and Structural... 2022The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein...
The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.
PubMed: 35782741
DOI: 10.1016/j.csbj.2022.06.051 -
Computational and Structural... 2022Shc SH2-domain binding protein 1 (SHCBP1), a protein specific binding to SH2 domain of Src homolog and collagen homolog (Shc), takes part in the regulation of various...
Shc SH2-domain binding protein 1 (SHCBP1), a protein specific binding to SH2 domain of Src homolog and collagen homolog (Shc), takes part in the regulation of various signal transduction pathways, which has been reported to be associated with tumorigenesis and progression. However, the pathological mechanisms are not completely investigated. Thus, this study aimed to comprehensively elucidate the potential functions of SHCBP1 in multiple cancer types. The comprehensive analyses for SHCBP1 in various tumors, including gene expression, diagnosis, prognosis, immune-related features, genetic alteration, and function enrichment, were conducted based on multiple databases and analysis tools. SHCBP1 was upregulated in most types of cancers. The results of qRT-PCR had confirmed that SHCBP1 mRNA was significantly upregulated in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC) cell lines. Based on the receiver operating characteristic (ROC) and survival analysis, SHCBP1 was considered as a potential diagnostic and prognostic biomarker. Furthermore, SHCBP1 expression was linked with tumor immunity and immunosuppressive microenvironment according to the correlation analysis of SHCBP1 expression with immune cells infiltration, immune checkpoint genes, and immune-related genes (MHC genes, chemokines, and chemokines receptors). Moreover, SHCBP1 expression correlated with tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens. The feature of SHCBP1 mutational landscape in pan-cancer was identified. Finally, we focused on investigating the clinical significance and the potential biological role of SHCBP1 in LUAD. Our study comprehensively uncovered that SHCBP1 could be identified as an immune-related biomarker for cancer diagnosis and prognosis, and a potential therapeutic target for tumor immunotherapy.
PubMed: 35782736
DOI: 10.1016/j.csbj.2022.06.039 -
The American Journal of Surgical... Sep 2022The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using...
The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using updated criteria were classifiable as: I. Ductal plate malformation related (63%); that is, cystic bile duct hamartoma or not otherwise specified-type benign biliary cyst (35 with polycystic liver disease). These were female predominant (F/M=2.4), large (10 cm), often multifocal with degenerative/inflammatory changes and frequently misclassified as "hepatobiliary cystadenoma." II. Neoplastic (13%); 27 (10.5%) had ovarian-type stroma (OTS) and qualified as mucinous cystic neoplasm (MCN) per World Health Organization (WHO). These were female, solitary, mean age 52, mean size 11 cm, and 2 were associated with carcinoma (1 in situ and 1 microinvasive). There were 3 intraductal papillary neoplasms, 1 intraductal oncocytic papillary neoplasm, 1 cystic cholangiocarcinoma, and 2 cystic metastasis. III. Infectious/inflammatory (12%). These included 23 hydatid cysts (including 2 Echinococcus alveolaris both misdiagnosed preoperatively as cancer), nonspecific inflammatory cysts (abscesses, inflammatory cysts: 3.4%). IV. Congenital (7%). Mostly small (<3 cm); choledochal cyst (5%), foregut cyst (2%). V. Miscellaneous (4%). In conclusion, hepatic cysts occur predominantly in women (3/1), are mostly (90%) non-neoplastic, and seldom (<2%) malignant. Cystic bile duct hamartomas and their relative not otherwise specified-type benign biliary cysts are frequently multifocal and often misdiagnosed as "cystadenoma/carcinoma." Defined by OTS, MCNs (the true "hepatobiliary cystadenoma/carcinoma") are solitary, constitute only 10.5% of hepatic cysts, and have a significantly different profile than the impression in the literature in that essentially all are perimenopausal females, and rarely associated with carcinoma (7%). Since MCNs can only be diagnosed by demonstration of OTS through complete microscopic examination, it is advisable to avoid the term "cystadenoma/cystadenocarcinoma" solely based on radiologic examination, and the following simplified terminology would be preferable in preoperative evaluation to avoid conflicts with the final pathologic diagnosis: (1) noncomplex (favor benign), (2) complex (in 3 subsets, as favor benign, cannot rule out malignancy, or favor malignancy), (3) malignant features.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Choledochal Cyst; Cystadenocarcinoma; Cystadenoma; Cysts; Diagnosis, Differential; Female; Humans; Liver Diseases; Male; Middle Aged; Pancreatic Neoplasms
PubMed: 35778790
DOI: 10.1097/PAS.0000000000001930 -
Frontiers in Immunology 2022Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2...
OBJECTIVE
Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2 in cancers.
METHODS
Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze the mRNA expression of ADA1 and ADA2 in human normal cells and tumor tissues. The enzyme assay was used to detect the ADA1 and ADA2 activities in serum from cancer patients. The Kaplan-Meier (KM) plotter was used to analyze the prognostic value of ADA1 and ADA2. TIMER2.0 was used to explore how ADA1 and ADA2 correlate with immune infiltration and immune checkpoints. cBioPortal database was used to investigate the mutations of ADA1 and ADA2. LinkedOmics was used to screen the ADA1 and ADA2 expression-related genes.
RESULTS
ADA1 was significantly increased in several tumor tissues, including cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), thymoma (THYM), and uterine carcinosarcoma (UCS). ADA2 expression was significantly increased in esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), OV, PAAD, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). There were no significant changes in serum ADA1 activities in most cancers, while serum ADA2 activities were increased in most cancers. For prognosis, high ADA1 expression was associated with the poor survival in several cancers, including esophageal squamous cell carcinoma (ESCC), HNSC, KIRC, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC). However, high ADA2 expression showed a favorable prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), HNSC, KIRC, KIRP, LUAD, OV, PAAD, sarcoma, and THYM. ADA1 showed a moderate positive correlation with multiple infiltrating immune cells in most cancers. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells. Function analysis showed that ADA1 expression-related genes were mainly enriched in cell division biological progression. However, ADA2-related genes were mainly associated with immune response.
CONCLUSION
As isoenzymes, ADA1 and ADA2 showed opposite prognostic values and different correlative patterns with immune infiltrating. These data demonstrated the distinct roles of ADA1 and ADA2 in cancer. ADA2 might act as a protective factor in cancer.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adenosine Deaminase; Carcinoma, Renal Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Head and Neck Neoplasms; Humans; Isoenzymes; Kidney Neoplasms; Lung Neoplasms; Melanoma; Pancreatic Neoplasms; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Melanoma, Cutaneous Malignant
PubMed: 35663977
DOI: 10.3389/fimmu.2022.903461 -
Gynecologic Oncology Jun 2022Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall...
OBJECTIVE
Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes.
METHODS
The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed.
RESULTS
Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0-176.6) versus 89.5 months (95% CI, 61.4-117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0-176.6) versus 78.0 months (95% CI, 57.6-98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9-166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS.
CONCLUSIONS
Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.
Topics: Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Female; Genomics; Humans; Mutation; Ovarian Neoplasms; Peritoneal Neoplasms
PubMed: 35606067
DOI: 10.1016/j.ygyno.2021.11.019 -
Journal of Cancer Research and... 2022Although papillary serous cyst adenocarcinoma of the ovary is a common tumor, the incidence of ovarian-type papillary serous cyst adenocarcinoma in the testis is rare....
Although papillary serous cyst adenocarcinoma of the ovary is a common tumor, the incidence of ovarian-type papillary serous cyst adenocarcinoma in the testis is rare. Based on medical documents, there are only about 50 cases reported about testicular and paratesticular serous tumors. Herein, we report a case of low-grade serous cyst adenocarcinoma of the testis that did unilateral orchiectomy and then came with retroperitoneal mass and lung metastasis. Chemotherapy was well tolerated, and now, after 1 year, he does not have any complaint.
Topics: Adenocarcinoma; Cystadenocarcinoma, Serous; Cysts; Female; Humans; Male; Middle Aged; Testicular Neoplasms
PubMed: 35381807
DOI: 10.4103/jcrt.JCRT_1153_19 -
Autopsy & Case Reports 2022Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included... (Review)
Review
Papillary cystadenocarcinoma of the salivary gland is a very rare malignant neoplasm accounting for only 2% of all salivary gland lesions. In 1991 it was first included as a separate entity in the World Health Organization (WHO) classification of salivary gland tumors and in 2017 WHO Classification, the tumor was clubbed as a sub-variant of adenocarcinoma, not otherwise specified. It most commonly occurs in the major salivary glands. Herein we report a case of salivary papillary cystadenocarcinoma in a 54-year-old female, who presented with rapid enlargement of the right parotid swelling. Based on radiology and fine-needle aspiration cytology, a working diagnosis of the malignant tumor involving the superficial lobe of the right parotid gland was made. In view of the malignant nature of the swelling, superficial parotidectomy was done. The histopathology and immunohistochemistry of the mass confirmed the diagnosis of papillary cystadenocarcinoma of the right parotid. With the revised 2017 WHO classification of salivary gland tumors, it is important to report all rare subtypes in order to understand their biology and behavior.
PubMed: 35252049
DOI: 10.4322/acr.2021.357 -
Gynecologic Oncology May 2022Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly...
PURPOSE/OBJECTIVES
Lymph node (LN) involvement is an important factor in guiding adjuvant treatment for patients with endometrial cancer. Risk factors for LN involvement are fairly well-established for endometrial adenocarcinoma, but it is not as well defined whether these factors similarly predict LN positivity in less common histologies.
MATERIALS/METHODS
Patients diagnosed with pathologic T1-T2 carcinosarcoma, clear cell, uterine papillary serous carcinoma (UPSC), and mixed histologic type endometrial cancer between 2004 and 2016 undergoing primary surgery with at least 1 lymph node sampled in the National Cancer Data Base were identified. Logistic regression was performed to identify primary pathologic tumor predictors of LN positivity. Nomograms were created to predict overall, pelvic only, and paraaortic with or without pelvic LN involvement.
RESULTS
Among 11,390 patients included, 1950 (18%) were node positive. On multivariable analysis, increasing pathologic tumor stage (pT2 versus pT1a, odds ratio [OR] 3.63, 95% confidence interval [CI] 3.15-4.18, p < 0.001), increase in tumor size per centimeter (OR 1.08, 95% CI 1.06-1.10, p < 0.001), and the presence of lymphovascular invasion (LVI) (OR 4.97, 95% CI 4.43-5.57, p < 0.001) were predictive of overall LN positivity. Relative to carcinosarcoma, both clear cell (OR 1.54, 95% CI 1.22-1.95, p < 0.001) and UPSC (OR 1.73, 95% CI 1.48-2.02, p < 0.001) histology were significantly associated with a higher risk of LN positivity while mixed histology was not (OR 1.07, 95% CI 0.92-1.24, p = 0.42).
CONCLUSION
Among patients with non-endometrioid endometrial cancer, predictors of LN positivity are similar to endometrial adenocarcinoma. The nomograms provided could be helpful in making adjuvant treatment decisions for these less common histologies.
Topics: Adjuvants, Immunologic; Carcinosarcoma; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Humans; Lymph Nodes; Nomograms
PubMed: 35216809
DOI: 10.1016/j.ygyno.2022.01.016 -
Journal of the Egyptian National Cancer... Feb 2022High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested...
BACKGROUND
High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested different prognosis. Addressing the presence of histopathological and immunohistochemical differences in HGSOC that parallel the molecular subtypes can help in tailoring the management protocol to improve therapeutic response and patient outcome.
METHODS
This retrospective study was conducted on 85 specimens for cases of HGSOC. Cases were classified according to histopathological findings into mesenchymal, proliferative, immunoreactive, and differentiated subtypes. Cases were immunostained with ER, PR, Ki67, CD8, E-cadherin, and vimentin.
RESULTS
By applying histopathological data, cases were subdivided into 4 groups; mesenchymal type represented by 25 cases, proliferative type which included 14 cases, the immunoreactive type included 14 cases, and differentiated type represented by 32 cases; 13 of them had SET features and 19 had papillary architectural features. A significant correlation was found between Ki67 and proliferative subtype, as well as between CD8 and immunoreactive subtype. ER showed significantly higher expression in proliferative subtype in the group treated by primary debulking. CD8 showed a significant correlation with solid endometroid transitional (SET) pattern in the group that underwent interval debulking. In terms of prognosis, the shortest median progression-free survival (PFS) was for mesenchymal subtype, while the longest median PFS was for differentiated subtype with SET architectural pattern with statistically significant correlation. No correlation was found between any of the studied parameters and overall survival.
CONCLUSION
Histopathological features and immunohistochemistry can help to stratify HGSOC into prognostic distinct groups.
Topics: Cystadenocarcinoma, Serous; Humans; Ovarian Neoplasms; Prognosis; Progression-Free Survival; Retrospective Studies
PubMed: 35138498
DOI: 10.1186/s43046-022-00104-9 -
Computational and Structural... 2022Cox proportional hazard regression (CPH) model relies on the proportional hazard (PH) assumption: the hazard of variables is independent of time. CPH has been widely...
BACKGROUND
Cox proportional hazard regression (CPH) model relies on the proportional hazard (PH) assumption: the hazard of variables is independent of time. CPH has been widely used to identify prognostic markers of the transcriptome. However, the comprehensive investigation on PH assumption in transcriptomic data has lacked.
RESULTS
The whole transcriptomic data of the 9,056 patients from 32 cohorts of The Cancer Genome Atlas and the 3 lung cancer cohorts from Gene Expression Omnibus were collected to construct CPH model for each gene separately for fitting the overall survival. An average of 8.5% gene CPH models violated the PH assumption in TCGA pan-cancer cohorts. In the gene interaction networks, both hub and non-hub genes in CPH models were likely to have non-proportional hazards. Violations of PH assumption for the same gene models were not consistent in 5 non-small cell lung cancer datasets (all kappa coefficients < 0.2), indicating that the non-proportionality of gene CPH models depended on the datasets. Furthermore, the introduction of log(t) or sqrt(t) time-functions into CPH improved the performance of gene models on overall survival fitting in most tumors. The time-dependent CPH changed the significance of log hazard ratio of the 31.9% gene variables.
CONCLUSIONS
Our analysis resulted that non-proportional hazards should not be ignored in transcriptomic data. Introducing time interaction term ameliorated performance and interpretability of non-proportional hazards of transcriptome data in CPH.
PubMed: 35070171
DOI: 10.1016/j.csbj.2022.01.004