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World Journal of Surgical Oncology Jun 2024The aim of this study is to investigate the risk factors for lateral cervical lymph node metastasis in papillary thyroid carcinoma (PTC).
OBJECTIVE
The aim of this study is to investigate the risk factors for lateral cervical lymph node metastasis in papillary thyroid carcinoma (PTC).
METHODS
Clinicopathological data (age, gender, Hashimoto's thyroiditis, preoperative circulating tumor cells (CTCs), multifocal, maximum lesion diameter, invaded capsule, T stage, and lymph node metastasis) of 830 PTC patients diagnosed and treated in Meizhou People's Hospital from June 2021 to April 2023 were collected. The related factors of lateral cervical lymph node metastasis were analyzed.
RESULTS
There were 334 (40.2%), and 103 (12.4%) PTC patients with central lymph node metastasis, and lateral cervical lymph node metastasis, respectively. Compared with patients without lateral cervical lymph node metastasis, PTC patients with lateral cervical lymph node metastasis had a higher proportion of multifocal, maximum lesion diameter > 1 cm, invaded capsule, T3-T4 stage. Regression logistic analysis showed that male (odds ratio (OR): 2.196, 95% confidence interval (CI): 1.279-3.769, p = 0.004), age < 55 years old (OR: 2.057, 95% CI: 1.062-3.988, p = 0.033), multifocal (OR: 2.759, 95% CI: 1.708-4.458, p < 0.001), maximum lesion diameter > 1 cm (OR: 5.408, 95% CI: 3.233-9.046, p < 0.001), T3-T4 stage (OR: 2.396, 95% CI: 1.241-4.626, p = 0.009), and invaded capsule (OR: 2.051, 95% CI: 1.208-3.480, p = 0.008) were associated with lateral cervical lymph node metastasis.
CONCLUSIONS
Male, age < 55 years old, multifocal, maximum lesion diameter > 1 cm, T3-T4 stage, and invaded capsule were independent risk factors for lateral cervical lymph node metastasis in PTC.
Topics: Humans; Male; Lymphatic Metastasis; Female; Middle Aged; Retrospective Studies; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Adult; Prognosis; Follow-Up Studies; Lymph Nodes; Neck; Aged; Thyroidectomy; Neoplasm Staging; Young Adult
PubMed: 38907249
DOI: 10.1186/s12957-024-03455-w -
Medicine Jun 2024The incidence of papillary thyroid carcinoma (PTC) has increased significantly in recent years, and for patients with metastatic and recurrent PTC, the options for...
The incidence of papillary thyroid carcinoma (PTC) has increased significantly in recent years, and for patients with metastatic and recurrent PTC, the options for treatment currently available are insufficient. To date, the exact molecular mechanism underlying PTC is still not fully understood. 5-Methylcytosine (m5C) RNA methylation is associated with the prognosis of a variety of tumors. However, the molecular mechanisms and biomarkers associated with m5C in the diagnosis, treatment, and prognosis of this disease have not been fully elucidated. Ten m5C regulators with significantly different expression levels were included in this study. Immune infiltration analysis revealed significant negative correlations between most of these regulators and regulatory T cells. TRDMT1, NSUN5, and NSUN6 had high weights and strong correlations in the protein-protein interaction network. Using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis, 1489 differentially expressed genes were screened from The Cancer Genome Atlas messenger RNA matrix, indicating that these differentially expressed genes were significantly enriched in various pathways and functions related to cancers. Four m5C regulators, NSUN2, NSUN4, NSUN6, and DNMT3B, were screened as prognostic markers by least absolute shrinkage and selection operator regression analysis, and NSUN2 and NSUN6 were identified as risk factors for poor prognosis. We found that the prognostic prediction model constructed using the m5C regulators NSUN2, NSUN4, NSUN6, and DNMT3B showed good prognostic prediction ability and diagnostic ability. This model was applied to predict the survival probability of patients with PTC, the prediction ability of 5-year survival was the best. The multi-factor prognostic prediction model combined with the tumor node metastasis stage and risk score grouping showed better prognostic predictive power.
Topics: Humans; Thyroid Cancer, Papillary; Prognosis; Thyroid Neoplasms; Biomarkers, Tumor; 5-Methylcytosine; Male; Female; Gene Expression Regulation, Neoplastic; Methylation; Middle Aged
PubMed: 38905403
DOI: 10.1097/MD.0000000000038623 -
Frontiers in Endocrinology 2024Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as , , and have been widely used in adult PTC. It is currently unclear whether these...
OBJECTIVES
Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as , , and have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC).
MATERIALS AND METHODS
The patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients.
RESULTS
A sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations and fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis.
CONCLUSION
mutation and fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians.
Topics: Humans; Female; Adolescent; Thyroid Cancer, Papillary; Male; Child; Thyroid Neoplasms; Mutation; Retrospective Studies; Proto-Oncogene Proteins B-raf; Adult; Middle Aged; Biomarkers, Tumor; Proto-Oncogene Proteins c-ret; High-Throughput Nucleotide Sequencing; DNA Mutational Analysis
PubMed: 38904052
DOI: 10.3389/fendo.2024.1405142 -
Journal of Translational Medicine Jun 2024The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and...
The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and often recurs, posing significant health and economic burdens. The role of iodine in the pathogenesis and advancement of thyroid cancer remains poorly understood. Circular RNAs (circRNAs) are recognized to function as competing endogenous RNAs (ceRNAs) that modulate gene expression and play a role in various cancer stages. Consequently, this research aimed to elucidate the mechanism by which circRNA influences the impact of iodine on PTC. Our research indicates that high iodine levels can exacerbate the malignancy of PTC via the circ_0004851/miR-296-3p/FGF11 axis. These insights into iodine's biological role in PTC and the association of circRNA with the disease could pave the way for novel biomarkers and potentially effective therapeutic strategies to mitigate PTC progression.
Topics: MicroRNAs; RNA, Circular; Humans; Thyroid Cancer, Papillary; Iodine; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Thyroid Neoplasms; Base Sequence
PubMed: 38902782
DOI: 10.1186/s12967-024-05405-2 -
Modern Pathology : An Official Journal... Jun 2024Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or...
Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or operative history. Its histopathological diversity can create diagnostic dilemmas and pathologists utilize morphological evaluation along with available immunohistochemical markers to navigate these challenges. Immunohistochemical assays currently do not designate or specify nephrogenic adenoma's potential putative cell of origin. Leveraging single-cell RNA sequencing technology, we nominated a principal cell collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for nephrogenic adenoma. Immunohistochemical characterization revealed L1CAM to be positive in all 35 (100%) patient samples of nephrogenic adenoma; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma in situ, prostatic adenocarcinoma, majority of high-grade urothelial carcinoma, and metastatic urothelial carcinoma. In the study, we also utilized single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for proximal tubule, loop of Henle, and distal tubule (including principal and intercalated cells) which can be used to perform nephronal mapping utilizing RNA in situ hybridization and immunohistochemistry technology. Employing this technique on nephrogenic adenoma we found enrichment of both principal cell marker L1CAM and, the proximal tubule types-A and -B cells markers, PDZKI1P1 and PIGR respectively. The cell type markers for the intercalated cell of distal tubules (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in nephrogenic adenoma. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between distal tubule principal cell (P) cells and nephrogenic adenoma. L1CAM expression will be of potential value in assisting surgical pathologists towards a diagnosis of nephrogenic adenoma in challenging patient samples.
PubMed: 38901674
DOI: 10.1016/j.modpat.2024.100540 -
World Journal of Clinical Cases Jun 2024The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly...
The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly disease. Premalignant lesions such as Intraductal Papillary Mucinous Neoplasms or Mucinous Cystic Neoplasms of the pancreas are detectable on imaging exams and this permits their management prior their invasive development. Pancreatic intraepithelial neoplasms (PanIN) are the most frequent precursors of pancreatic adenocarcinoma (PDAC), and its particular type PanIN high-grade represents the malignant non-invasive form of PDAC. Unfortunately, PanINs are not detectable on radiologic exams. Nevertheless, they can associate indirect imaging signs which would rise the diagnostic suspicion. When this suspicion is established, the patient will be enrolled in a follow-up strategy that includes performing of blood test and serial imaging test such as computed tomography or magnetic resonance imaging, which will cost in the best-case scenario a burden of healthcare systems, and potential mortality in the worst-case scenario when the patient underwent resection surgery, worthless when there is no moderate or high grade dysplasia in the final histopathology. This issue will be avoid having at its disposal a diagnostic technique capable of detecting high-grade PanIN lesions, such is the cytology of pancreatic juice obtained by nasopancreatic intubation. Herein, we review the possibility of detection of early malignant lesions before they become invasive PADC.
PubMed: 38898835
DOI: 10.12998/wjcc.v12.i17.2935 -
Cureus May 2024Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver,...
Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver, thyroid, and bile duct cancer due to its crucial role in cell cycle regulation and cell division. Nevertheless, it is mostly investigated at the genetic level, but it is still poorly studied on pan-cancer analysis as a biomarker and this study shows its significant potential diagnostic and prognostic characteristics. However, this study aims to investigate the role of CDKN2A as a diagnostic and prognostic biomarker across various types of cancer focusing primarily on colon adenocarcinoma (COAD). Methods We investigated CDKN2A gene expression in a pan-cancer analysis across different types of cancer to show its diagnostic potential characteristics by using various bioinformatic tools, including Tumor Immune Estimation Resource (TIMER) 2.0, Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. TIMER was used to profile gene expression across 32 types of cancer composed of 10,000 RNA-seq samples obtained from the Cancer Genome Atlas (TCGA) and to analyze the tumor-infiltrating immune cells. In addition, GEPIA and UALCAN were further used to analyze gene expression, in terms of gene regulation, pathological stages, and clinical parameters, including gender, age, and race. Therefore, we used GEPIA, UALCAN, and Kaplan-Meier plotter particularly across adenocarcinoma to investigate CDKN2A prognosis by studying its high expression association with the patient's overall survival rate to show the tumor progression. Then, we looked into the genetic alteration of CDKN2A by using the cBio Cancer Genomics Portal (cBioPortal), including 10 pan-cancer studies. We concluded the analysis with gene validation by using a public cohort in Gene Expression Omnibus (GEO). Results CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in five cancers, which were commonly identifiable in three databases, including breast invasive carcinoma (p < 0.001), kidney chromophobe (p < 0.001), kidney renal clear cell carcinoma (p < 0.001), kidney renal papillary cell carcinoma (p < 0.001), and COAD (p < 0.001). The upregulation was significantly different in association with pathogenic stages II and III (pr(>F) = 0.00234) which was identifiable significantly in COAD more than in other cancers. The gene showed a high upregulation in association with poor prognosis of patient survival in three cancers, including COAD (log-rank p = 0.011), mesothelioma (log-rank p = 5.9e-07), and liver hepatocellular carcinoma (log-rank p = 0.0045). Therefore, COAD was the only comprehensively analyzed tumor to show a diagnostic and prognostic potential characteristic during high upregulation of CDKN2A. Furthermore, CDKN2A displayed a rare mutation in the form of deep deletion (9%) and revealed an upregulation associated with CD4+ T cells (p = 0.0108), macrophage (p = 0.0073), and neutrophils (p = 0.0272) as immune cells infiltrating COAD. Conclusion Our study demonstrates the pan-cancer relevance of CDKN2A and revealed a novelty in showing CDKN2A underscores its potential as a diagnostic prognostic biomarker in COAD since CDKN2A is mostly studied at a genetic level across COAD.
PubMed: 38894777
DOI: 10.7759/cureus.60586 -
Cancers Jun 2024Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and...
Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.
PubMed: 38893252
DOI: 10.3390/cancers16112133 -
Cancers May 2024Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The...
Oncological Outcomes and Patterns of Recurrence after the Surgical Resection of an Invasive Intraductal Papillary Mucinous Neoplasm versus Primary Pancreatic Ductal Adenocarcinoma: An Analysis from the German Cancer Registry Group of the Society of German Tumor Centers.
BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The available literature has shown controversial results regarding prognosis and clinical outcomes after the resection of invasive IPMN.
AIMS
This study aims to characterize the oncologic outcomes and metastatic progression pattern after the resection of non-metastatic invasive IPMN.
METHODS
Data were obtained from 24 clinical cancer registries participating in the German Cancer Registry Group of the Society of German Tumor Centers (ADT). Patients with invasive IPMN ( = 217) as well as PDAC ( = 5794) between 2000 and 2021 were included and compared regarding oncological outcomes.
RESULTS
Invasive IPMN was significantly smaller in size ( < 0.001) and of a lower tumor grade ( < 0.001), with fewer lymph node metastases ( < 0.001), lymphangiosis ( < 0.001), and consequently a higher R0 resection rate (88 vs. 74%) compared to PDAC. Moreover, invasive IPMN was associated with fewer local (11 vs. 15%) and distant recurrences (29 vs. 46%) and metastasized more frequently in the lungs only (26% vs. 14%). Invasive IPMN was associated with a longer median OS (29 vs. 19 months) and DFS (31 vs. 15 months) compared to PDAC and stayed independently prognostic in multivariable analyses. These survival differences were most pronounced in early tumor stages. Interestingly, postoperative chemotherapy was not associated with improved overall survival in surgically resected invasive IPMN.
CONCLUSIONS
Invasive IPMN is a rare pancreatic entity with increasing incidence in Germany. It is associated with favorable histopathological features at the time of resection and longer OS and DFS compared to PDAC, particularly before the locoregional spread has occurred. Invasive IPMNs are associated with lung-only metastasis. The benefit of postoperative chemotherapy after the resection of invasive IPMN remains uncertain.
PubMed: 38893136
DOI: 10.3390/cancers16112016 -
Clinical Epigenetics Jun 2024Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies....
BACKGROUND
Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies. MiR-570-3p has been shown to have a regulatory function in various cancers. However, studies of the regulatory function of miR-570-3p and a direct link between estrogen (especially estradiol E2) and miR-570-3p in PTC have not been done.
METHODS
Expression of miR-570-3p and its downstream target DPP4 in PTC tissues and cells was predicted using bioinformatics and validated by qRT-PCR and western blot assays. We then performed a series of gain-and-loss experiments to assess the functional significance of miR-570-3p/DPP4 axis in PTC progression in vitro and in vivo. Additionally, the methylation of the miR-570-3p promoter region was examined via bioinformatics analysis and MSP. Finally, the effects of E2 on PTC progression and the correlation between DNMT1/DNMT3A and EZH2 were predicted by bioinformatic tools and proved by luciferase reporter, ChIP, and co-IP assays.
RESULTS
In PTC tumor tissues and cell lines, there was a lower expression level and a higher methylation level of miR-570-3p compared to normal tissues and cell lines. DPP4 was identified as the downstream target of miR-570-3p. Overexpression of miR-570-3p reduced the proliferative, migratory, and invasive capabilities, and promoted apoptosis, while overexpression of DPP4 reversed these effects in PTC cells. It was also discovered that DNMT1 and DNMT3A increased the CpG methylation level of the miR-570-3p promoter in an EZH2-dependent manner, which led to decreased expression of miR-570-3p. Furthermore, we observed that estrogen (E2) enhanced the methylation of miR-570-3p and suppressed its expression levels, resulting in augmented tumor growth in vivo in PTC.
CONCLUSION
Estrogen regulates the EZH2/DNMTs/miR-570-3p/DPP4 signaling pathway to promote PTC progression.
Topics: Humans; MicroRNAs; DNA (Cytosine-5-)-Methyltransferase 1; Enhancer of Zeste Homolog 2 Protein; Thyroid Cancer, Papillary; Dipeptidyl Peptidase 4; DNA Methyltransferase 3A; Cell Line, Tumor; Thyroid Neoplasms; Estrogens; Gene Expression Regulation, Neoplastic; Female; Mice; DNA Methylation; Animals; DNA (Cytosine-5-)-Methyltransferases; Cell Proliferation; Male; Promoter Regions, Genetic
PubMed: 38890707
DOI: 10.1186/s13148-024-01685-z