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BMC Cancer Sep 2023Guidelines recommend total thyroidectomy (TT) to facilitate radioactive ablation and serological follow-up for intermediate- to high-risk papillary thyroid carcinoma...
BACKGROUND
Guidelines recommend total thyroidectomy (TT) to facilitate radioactive ablation and serological follow-up for intermediate- to high-risk papillary thyroid carcinoma (PTC). However, the association between surgical extent and tumor recurrence in these patients has not been well validated. We aimed to examine the association between the extent of surgery and recurrence in patients with completely resected unilateral intermediate- to high-risk PTC.
METHODS
Patients with completely resected unilateral PTC from 2000 to 2017 in a single institute were reviewed. Those who had extrathyroidal extension (ETE) or lymph node metastasis (LNM, cN1 or pN1 > 5 lymph nodes involved) were included for analysis. Cox proportional hazards models were applied to measure the association between surgical extent and recurrence-free survival (RFS) while adjusting for patient demographic, clinicopathological and treatment variables.
RESULTS
A total of 4550 patients (mean[SD] age, 43.0[11.7] years; 3379 women[74.3%]) were included. Of these patients, 2262(49.7%), 656(14.4%), 1032(22.7%), and 600 (13.2%) underwent lobectomy, TT, lobectomy + neck dissection (ND) and TT + ND, respectively. With a median follow-up period of 68 months, after multivariate adjustment, lobectomy was associated with a compromised RFS compared with other surgical extents (HR[95%CI], TT 0.537[0.333-0.866], P = 0.011, lobectomy + ND 0.531[0.392-0.720] P < 0.0001, TT + ND 0.446[0.286-0.697] P < 0.0001). RFS was similar between the two extents with ND (lobectomy + ND, HR [95%CI], 1.196 [0.759-1.885], P = 0.440).
CONCLUSION
Lobectomy alone is associated with an elevated recurrence risk in patients with unilateral intermediate- to high-risk PTC compared with larger surgical extents. However, lobectomy and ND may provide similar tumor control compared with the conventional approach of TT and ND.
Topics: Humans; Female; Adult; Thyroid Cancer, Papillary; Thyroidectomy; Lymph Nodes; Lymphatic Metastasis; Thyroid Neoplasms
PubMed: 37723469
DOI: 10.1186/s12885-023-11307-1 -
Frontiers in Endocrinology 2023
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule
PubMed: 37786792
DOI: 10.3389/fendo.2023.1283397 -
Cancer Science Dec 2023Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis....
Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.
Topics: Humans; Cell Line, Tumor; Thyroid Neoplasms; Thyroid Cancer, Papillary; Carcinogenesis; Cell Transformation, Neoplastic; Cell Proliferation; Tetraspanins; Cell Movement; Gene Expression Regulation, Neoplastic; MicroRNAs
PubMed: 37750019
DOI: 10.1111/cas.15970 -
Journal of Cancer Research and Clinical... Dec 2023Characterizing tumor microenvironment using single-cell RNA sequencing has been a promising strategy for cancer diagnosis and treatment. However, a few studies have...
BACKGROUND
Characterizing tumor microenvironment using single-cell RNA sequencing has been a promising strategy for cancer diagnosis and treatment. However, a few studies have focused on diagnosing papillary thyroid cancer (PTC) through this technology. Therefore, our study explored tumor microenvironment (TME) features and identified potential biomarkers to establish a diagnostic model for papillary thyroid cancer.
METHODS
The cell types were identified using the markers from the CellMarker database and published research. The CellChat package was conducted to analyze the cell-cell interaction. The SCEVAN package was used to identify malignant thyroid cells. The SCP package was used to perform multiple single-cell downstream analyses, such as GSEA analysis, enrichment analysis, pseudotime trajectory analysis, and differential expression analysis. The diagnostic model of PTC was estimated using the calibration curves, receiver operating characteristic curves, and decision curve analysis. RT-qPCR was performed to validate the expression of candidate genes in human papillary thyroid samples.
RESULTS
Eight cell types were identified in the scRNA-seq dataset by published cell markers. Extensive cell-cell interactions like FN1/ITGB1 existed in PTC tissues. We identified 26 critical genes related to PTC progression. Further, eight subgroups of PTC tumor cells were identified and exhibited high heterogeneity. The MDK/LRP1, MDK/ALK, GAS6/MERTK, and GAS6/AXL were identified as potential ligand-receptor pairs involved in the interactions between fibroblasts/endothelial cells and tumor cells. Eventually, the diagnostic model constructed by TRPC5, TENM1, NELL2, DMD, SLC35F3, and AUTS2 showed a good efficiency for distinguishing the PTC and normal tissues.
CONCLUSIONS
Our study comprehensively characterized the tumor microenvironment in papillary thyroid cancer. Through combined analysis with bulk RNA-seq, six potential diagnostic biomarkers were identified and validated. The diagnostic model we constructed was a promising tool for PTC diagnosis. Our findings provide new insights into the heterogeneity of thyroid cancer and the theoretical basis for diagnosing thyroid cancer.
Topics: Humans; Thyroid Cancer, Papillary; Endothelial Cells; Tumor Microenvironment; Thyroid Neoplasms; RNA-Seq; Biomarkers; Biomarkers, Tumor
PubMed: 37733241
DOI: 10.1007/s00432-023-05420-8 -
Scientific Reports Nov 2023Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer. This study aims to investigate genomic and...
Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer. This study aims to investigate genomic and clinicopathological characteristics of EBVaGC according to the histological pattern. We retrospectively collected 18 specimens of surgically resected EBVaGCs. Whole-exome sequencing was performed for all cases. Moreover, PD-L1 expression and tumor-infiltrating lymphocyte (TIL) percentage were investigated. Among 18 EBVaGCs, 10 cases were of intestinal histology, 3 were of poorly cohesive histology, and the remaining 5 were of gastric carcinoma with lymphoid stroma histology. Whole-exome sequencing revealed that EBVaGCs with intestinal histology harbored pathogenic mutations known to frequently occur in tubular or papillary adenocarcinoma, including TP53, KRAS, FBXW7, MUC6, ERBB2, CTNNB1, and ERBB2 amplifications. One patient with poorly cohesive carcinoma histology harbored a CDH1 mutation. Patients with EBVaGCs with intestinal or poorly cohesive carcinoma histology frequently harbored driver mutations other than PIK3CA, whereas those with EBVaGCs with gastric carcinoma with lymphoid stroma histology lacked other driver mutations. Moreover, the histological pattern of EBVaGCs was significantly associated with the levels of TILs (P = 0.005) and combined positive score (P = 0.027). In conclusion, patients with EBVaGCs with different histological patterns exhibited distinct genetic alteration, PD-L1 expression, and degree of TILs.
Topics: Humans; B7-H1 Antigen; Carcinoma; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Retrospective Studies; Stomach Neoplasms
PubMed: 37945587
DOI: 10.1038/s41598-023-45930-6 -
Oncogene Jan 2024Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the...
Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a Braf-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine Braf mutation, equivalent to Braf in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. Braf-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed Braf oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.
Topics: Animals; Mice; Carcinogenesis; Mutation; Organoids; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 37985676
DOI: 10.1038/s41388-023-02889-y -
In Vivo (Athens, Greece) 2023Programmed death-ligand 1 (PD-L1) is a component of the tumor microenvironment, which is closely involved in the occurrence and development of tumors. We investigated...
AIM
Programmed death-ligand 1 (PD-L1) is a component of the tumor microenvironment, which is closely involved in the occurrence and development of tumors. We investigated the correlation between the expression of PD-L1 and ultrasound characteristics in papillary thyroid carcinoma (PTC) and its effect on recurrence.
PATIENTS AND METHODS
Fifty-two patients at the Department of General Surgery of Qingdao Municipal Hospital underwent thyroid ultrasonic examination before surgery and their clinicopathological variables were collected. Then, immunohistochemistry staining was conducted to evaluate the PD-L1 expression in tumors and adjacent normal tissues. The correlations of PD-L1 expression with clinicopathological and ultrasound characteristics were analyzed.
RESULTS
The expression of PD-L1 was positive in 59.7% (40/67) of PTC tumor tissues. In clinicopathological analyses, PD-L1 positivity was related to multifocality of tumors (p=0.031). In analyses of ultrasound characteristics, the expression of PD-L1 was positively correlated with halo sign (p=0.035), capsular invasion (p=0.003), microcalcification (p=0.02), and recurrence (p=0.009). In multivariate logistic analysis of ultrasonic characteristics and recurrence of thyroid carcinoma, microcalcification [odds ratio=13.349, 95% confidence interval (CI)=2.052-86.832, p=0.007] and the halo sign (odds ratio=15.273, 95% CI=1.451-160.747, p=0.023) were factors associated with recurrence of PTC. In the multivariate Cox regression analysis, positive PD-L1 staining [hazard ratio (HR)=5.031, 95% CI=1.092-23.172, p=0.038] and a halo sign (HR=4.998, 95% CI=1.084-23.051, p=0.039) were independent predictors for poorer recurrence-free survival. Positive expression of PD-L1 predicted worse recurrence-free survival in the subgroup of patients with a halo sign (HR=6.537, 95% CI=1.863-22.94, p=0.037).
CONCLUSION
Positive expression of PD-L1 in PTC affects the clinical and ultrasonic characteristics of the tumor and may negatively affect the prognosis of patients with PTC.
Topics: Humans; Thyroid Cancer, Papillary; B7-H1 Antigen; Thyroid Neoplasms; Prognosis; Calcinosis; Neoplasm Recurrence, Local; Tumor Microenvironment
PubMed: 37905619
DOI: 10.21873/invivo.13396 -
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 -
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