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Scientific Reports Feb 2024Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in...
Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in cardiac adenocarcinoma, breast cancer, gastric cancer and colorectal cancer, but the systematic analysis of PAQR3 in tumors is currently lacking. The objective of this study was to investigate the prognostic and therapeutic value of PAQR3 in 31 tumors. Through the analysis of TCGA, UALCAN, GEO, GEPIA2, TIMER, Kaplan-Meier plotter, TISIDB and other databases, it was found that the expression level of PAQR3 changed significantly in different tumor types, and the expression level of Neuroblastoma was very high. And the level of Prostate adenocarcinoma is low. In addition, the expression level of PAQR3 in Cholangiocarcinoma, Esophageal carcinoma, Head and neck squamous carcinoma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma and Lung squamous cell carcinoma was significantly higher than that in normal tissues. However, the expression level of PAQR3 in Breast Cancer, Kidney Renal Clear Cell Carcinoma, Kidney renal papillary cell carcinoma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Thyroid Cancer and Uterine Corpus Endometrial Carcinoma was lower than that in normal tissues. Subsequently, we explored the value of PAQR3 as a prognostic indicator of cancer. In Acute Myeloid Leukemia, Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Kidney Chromophobe, and Thyroid Cancer, PAQR3 expression was positively correlated with OS and DSS, while in Rectum Adenocarcinoma, PAQR3 expression was negatively correlated with OS. PAQR3 high expression group Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Uveal Melanoma, Kidney Chromophobe and DFI were positively correlated. PAQR3 can be used as a risk factor for the prognosis of multiple tumors. Then, we discussed the correlation between PAQR3 and immunology, and found that PAQR3 has a wide range of mutations in various tumor types, the most common mutation type is missense mutation, and common mutation types also include amplification, depth deletion, splicing, truncation and structural variation. Among the tumor samples with PAQR3 alterations, mutation occurred in all tumor samples except prostate adenocarcinoma and adrenal cortical carcinoma, head and neck squamous cell carcinoma, brain low-grade glioma, and kidney clear cell carcinoma, while esophageal adenocarcinoma had the highest total alteration frequency. PAQR3 was strongly associated with CNV in 18 tumors, particularly in Ovarian cancer, Lung squamous cell carcinoma, and Adenoid cystic carcinoma. On the other hand, PAQR3 has a higher SNV frequency in Uterine Corpus Endometrial Carcinoma, Skin Cutaneous Melanoma and Lung Adenocarcinoma, among which Uterine Corpus Endometrial Carcinoma has the highest SNV frequency. These results showed that PAQR3 expression levels were significantly correlated with tumor mutation load, microsatellite instability, neoantigens, and purity. In summary, PAQR3 can affect the tumor microenvironment and has potential for chemotherapy. Finally, we investigated the role of PAQR3 in tumor resistance and found that the expression of PAQR3 affects the efficacy of multiple chemotherapy drugs. Based on these studies, we found that PAQR3 plays an important role in cancer and has potential in tumor diagnosis and prognosis.
Topics: Child; Female; Humans; Male; Adenocarcinoma; Adenocarcinoma of Lung; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Endometrial Neoplasms; Glioblastoma; Glioma; Kidney Neoplasms; Lung Neoplasms; Melanoma; Prognosis; Prostatic Neoplasms; Skin Neoplasms; Thyroid Neoplasms
PubMed: 38321173
DOI: 10.1038/s41598-024-53489-z -
JAMA Otolaryngology-- Head & Neck... Sep 2023Fear is commonly experienced by individuals newly diagnosed with papillary thyroid cancer (PTC).
IMPORTANCE
Fear is commonly experienced by individuals newly diagnosed with papillary thyroid cancer (PTC).
OBJECTIVE
To explore the association between gender and fears of low-risk PTC disease progression, as well as its potential surgical treatment.
DESIGN, SETTING, AND PARTICIPANTS
This single-center prospective cohort study was conducted at a tertiary care referral hospital in Toronto, Canada, and enrolled patients with untreated small low risk PTC (<2 cm in maximal diameter) that was confined to the thyroid. All patients had a surgical consultation. Study participants were enrolled between May 2016 and February 2021. Data analysis was performed from December 16, 2022, to May 8, 2023.
EXPOSURES
Gender was self-reported by patients with low-risk PTC who were offered the choice of thyroidectomy or active surveillance. Baseline data were collected prior to the patient deciding on disease management.
MAIN OUTCOMES AND MEASURES
Baseline patient questionnaires included the Fear of Progression-Short Form and Surgical Fear (referring to thyroidectomy) questionnaires. The fears of women and men were compared after adjustment for age. Decision-related variables, including Decision Self-Efficacy, and the ultimate treatment decisions were also compared between genders.
RESULTS
The study included 153 women (mean [SD] age, 50.7 [15.0] years) and 47 men (mean [SD] age, 56.3 [13.8] years). There were no significant differences in primary tumor size, marital status, education, parental status, or employment status between the women and men. After adjustment for age, there was no significant difference observed in the level of fear of disease progression between men and women. However, women reported greater surgical fear compared with men. There was no meaningful difference observed between women and men with respect to decision self-efficacy or the ultimate treatment choice.
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with low-risk PTC, women reported a higher level of surgical fear but not fear of the disease compared with men (after adjustment for age). Women and men were similarly confident and satisfied with their disease management choice. Furthermore, the decisions of women and men were generally not significantly different. The context of gender may contribute to the emotional experience of being diagnosed with thyroid cancer and its treatment perception.
Topics: Humans; Female; Male; Middle Aged; Thyroid Cancer, Papillary; Cohort Studies; Prospective Studies; Sex Factors; Thyroid Neoplasms; Thyroidectomy; Disease Progression; Fear
PubMed: 37410454
DOI: 10.1001/jamaoto.2023.1642 -
Cureus Sep 2023Papillary adenocarcinoma (PA) of the lung is a specific form of lung cancer characterized by papillary structures in tumor cells. This type of cancer is relatively rare...
Papillary adenocarcinoma (PA) of the lung is a specific form of lung cancer characterized by papillary structures in tumor cells. This type of cancer is relatively rare and has distinct pathological and radiological features that differentiate it from other types of lung adenocarcinomas. Determining the specific subtype of adenocarcinoma is a crucial factor in the choice of chemotherapy treatment. Detecting PA is fundamental, as it has both prognostic and therapeutic implications for patients with lung carcinoma. In this paper, we discuss two cases of young patients diagnosed with PA of the lung. The cases we present are particularly intriguing due to the relatively young age of the patients.
PubMed: 37809161
DOI: 10.7759/cureus.44838 -
Frontiers in Endocrinology 2023Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.
METHODS
Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.
RESULTS
In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.
CONCLUSION
This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.
Topics: Humans; Thyroid Cancer, Papillary; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Thyroid Neoplasms; Lymphatic Metastasis; Prevalence; Carcinoma, Papillary; Mutation
PubMed: 38047109
DOI: 10.3389/fendo.2023.1273498 -
Cell Death & Disease Jan 2024Cancer cells alter their metabolism and epigenetics to support cancer progression. However, very few modulators connecting metabolism and epigenetics have been...
Cancer cells alter their metabolism and epigenetics to support cancer progression. However, very few modulators connecting metabolism and epigenetics have been uncovered. Here, we reveal that serine hydroxymethyltransferase-2 (SHMT2) generates S-adenosylmethionine (SAM) to epigenetically repress phosphatase and tensin homolog (PTEN), leading to papillary thyroid cancer (PTC) metastasis depending on activation of AKT signaling. SHMT2 is elevated in PTC, and is associated with poor prognosis. Overexpressed SHMT2 promotes PTC metastasis both in vitro and in vivo. Proteomic enrichment analysis shows that AKT signaling is activated, and is positively associated with SHMT2 in PTC specimens. Blocking AKT activation eliminates the effects of SHMT2 on promoting PTC metastasis. Furthermore, SHMT2 expression is negatively associated with PTEN, a negative AKT regulator, in PTC specimens. Mechanistically, SHMT2 catalyzes serine metabolism and produces activated one-carbon units that can generate SAM for the methylation of CpG islands in PTEN promoter for PTEN suppression and following AKT activation. Importantly, interference with PTEN expression affects SHMT2 function by promoting AKT signaling activation and PTC metastasis. Collectively, our research demonstrates that SHMT2 connects metabolic reprogramming and epigenetics, contributing to the poor progression of PTC.
Topics: Humans; Thyroid Cancer, Papillary; Proto-Oncogene Proteins c-akt; Thyroid Neoplasms; Proteomics; Epigenesis, Genetic; Cell Proliferation; Gene Expression Regulation, Neoplastic; Cell Line, Tumor
PubMed: 38272883
DOI: 10.1038/s41419-024-06476-1 -
Journal of Ethnopharmacology May 2024Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer with a rising global incidence. Despite favorable prognoses, a significant recurrence rate...
ETHNOPHARMACOLOGICAL RELEVANCE
Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer with a rising global incidence. Despite favorable prognoses, a significant recurrence rate persists. Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, has been historically used for thyroid-related disorders. However, its therapeutic effects and mechanisms of action on PTC remain unclear.
AIM OF THE STUDY
To explore the potential therapeutic effects, principal active components, and molecular mechanisms of DBL in the treatment of PTC through network pharmacology and molecular docking, with experimental validation conducted to corroborate these findings.
MATERIALS AND METHODS
The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was utilized as a systematic tool for collecting and screening the phytochemical components of DBL, and for establishing associations between these components and molecular targets. Based on this, network data was visually processed using Cytoscape software (version 3.8.0). Concurrently, precise molecular docking studies of the principal active components of DBL and their corresponding targets were conducted using Autodock software. Additionally, PTC-related genes were selected through the GeneCards and GEO databases. We further employed the DAVID bioinformatics resources to conduct comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the intersecting genes between DBL and PTC. These analyses aid in predicting the potential therapeutic actions of DBL on PTC and its mechanisms of action. To validate these findings, corresponding in vitro experimental studies were also conducted.
RESULTS
In this investigation, 14 bioactive compounds of DBL and 195 corresponding molecular targets were identified, with 127 common targets shared between DBL and PTC. Molecular docking revealed strong binding affinities between major bioactive compounds and target proteins. GO enrichment analysis unveiled key processes involved in DBL's action. KEGG analysis highlighted DBL's modulation of the PI3K/AKT signaling pathway. Experimental outcomes demonstrated DBL's potential in inhibiting PTC cell proliferation and migration, suppressing PI3K/AKT pathway activation, and promoting ferroptosis.
CONCLUSION
In conclusion, DBL offers a multifaceted therapeutic approach for PTC, targeting multiple molecular entities and influencing diverse biological pathways. Network pharmacology and molecular docking shed light on DBL's potential utility in PTC treatment, substantiated by experimental validation. This study contributes valuable insights into using DBL as a promising therapeutic agent for PTC management.
Topics: Thyroid Cancer, Papillary; Dioscorea; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Ferroptosis; Molecular Docking Simulation; Thyroid Neoplasms; Drugs, Chinese Herbal
PubMed: 38387682
DOI: 10.1016/j.jep.2024.117912 -
Cell Death & Disease Dec 2023Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying...
Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; RNA, Long Noncoding; Protein Kinase C-theta; Neoplasm Recurrence, Local; Fasting; Cell Proliferation; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; MicroRNAs; Cell Movement; Protein-Arginine N-Methyltransferases
PubMed: 38092752
DOI: 10.1038/s41419-023-06348-0 -
Journal of Clinical Pathology Mar 2024To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma.
AIMS
To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma.
METHODS
Immunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and gene rearrangement in adenocarcinoma from different organs.
RESULTS
The results showed that claudin18.2 expression was found in 68% (27 of 40) of lung mucinous adenocarcinoma, 52% (16 of 31) of cholangiocarcinoma, 2% (10 of 423) of colorectal adenocarcinoma tissue microarray, 27% (6 of 22) of colorectal mucinous adenocarcinoma and 30% (3 of 10) of cervical adenocarcinoma, but not in all 39 cases of invasive breast adenocarcinoma by immunohistochemistry staining. There was significantly positive correlation between ratio of claudin18.2-positive carcinoma cells and staining intensity in lung mucinous adenocarcinoma and cholangiocarcinoma. Claudin18.2 expression was much more in female patients than male patients with lung mucinous adenocarcinoma. In addition, cholangiocarcinoma with claudin18.2 expression was more aggressive and had perineural invasion. Intraductal papillary neoplasm of the bile duct and epithelial dysplasia of the adjacent bile in cholangiocarcinoma also showed claudin18.2 expression. All three cases of cervical adenocarcinoma with claudin18.2 expression were moderately differentiated adenocarcinoma including one human papillomavirus (HPV)-associated carcinoma, two non-HPV-associated and gastric-type carcinoma. gene rearrangement was not found in all 22 cases with high claudin18.2 expression by FISH.
CONCLUSIONS
Our results suggest claudin18.2 might be a potential biomarker for targeted therapy on lung mucinous adenocarcinoma, cholangiocarcinoma, colorectal mucinous adenocarcinoma and gastric-type cervical adenocarcinoma.
PubMed: 38548320
DOI: 10.1136/jcp-2023-209268 -
Frontiers in Endocrinology 2023Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine...
PURPOSE
Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients.
METHODS
OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis.
RESULTS
Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, =0.001) and P16 (OR=5.65, <0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, <0.001) and H4K16 (OR=6.03, <0.001) acetylation.
CONCLUSION
The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.
Topics: Humans; Thyroid Nodule; Lysine; DNA Methylation; Thyroid Neoplasms; Thyroid Cancer, Papillary; Epigenesis, Genetic; Pesticides
PubMed: 37560303
DOI: 10.3389/fendo.2023.1130794 -
World Journal of Surgical Oncology Aug 2023Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of malignant neoplasms. We aimed to investigate the clinicopathological...
PURPOSES
Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of malignant neoplasms. We aimed to investigate the clinicopathological characteristics of iPCN patients and to develop nomograms for individual survival prediction after radical surgery.
METHODS
Data of patients diagnosed with iPCN and pancreatic ductal adenocarcinoma (PDAC) between 2000 and 2018 from the SEER database were retrieved. The differences in clinical outcomes were evaluated using the Kaplan-Meier analysis. Nomograms were proposed based on the Cox regression model and internally validated by C-index, area under the curve (AUC) value, and calibration plot.
RESULTS
A total of 7777 iPCN patients and 154,336 PDAC patients were enrolled. Most neoplasms were advanced, with 63.1% at stage IV. The 3-year overall survival (OS) and cancer-specific survival (CSS) rates in surgical patients were as follows: 45.7% and 50.1% for invasive intraductal papillary mucinous neoplasm (IPMN), 54.8% and 59.3% for invasive mucinous cystic neoplasm (MCN), 97.8% and 98.2% for invasive solid pseudopapillary neoplasm (SPN), 88.9% and 88.9% for invasive serous cystic neoplasm (SCN), and 27.3% and 30.5% for PDAC. Subgroup analyses showed no clinical benefit from chemotherapy or radiotherapy in lymph node-negative iPCN patients who underwent surgery. The following variables associated with OS and CSS were identified: age, race, chemotherapy, radiotherapy, histologic type, pathological grade, regional nodes examined, and T, N, and M stage. The nomograms had good discrimination and calibration by internal validation, with an AUC value of 0.800 for 3-year OS and 0.814 for 3-year CSS.
CONCLUSION
Our study showed that the prognosis of iPCN patients was significantly better than PDAC patients. The proposed nomograms demonstrated substantially better discrimination and calibration.
Topics: Humans; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Carcinoma, Pancreatic Ductal
PubMed: 37612715
DOI: 10.1186/s12957-023-03145-z