Serum Biochemical Markers for Medullary Thyroid Carcinoma: An Update.

Introduction: Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC. Methods: A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers. Results: The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management. Conclusion: Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.

BRAFV600E mutation does not predict lymph node metastases and recurrence in Chinese papillary thyroid microcarcinoma patients.

OBJECT: Previous studies suggest BRAFV600E mutation is a marker for poor prognosis in papillary thyroid cancer, however, its ability to further risk stratify papillary thyroid microcarcinoma (PTMC) remains controversial. We aimed to explore the association between BRAFV600E mutation and the clinicopathological features and recurrence in Chinese PTMC patients. METHODS: We retrospectively reviewed 2094 PTMC patients who underwent surgery and had a valid BRAFV600E mutation test result. Among them, 1292 patients had complete follow-up data. The mutation incidence was determined. Moreover, the clinicopathological characteristics, disease-free survival (DFS), and response to therapy distribution were compared between the mutation and non-mutation groups. RESULTS: BRAFV600E mutation was observed in 90.6 % of all patients and 89.2 % of patients with complete follow-up data. No significant difference was observed in lymph node metastases (LNM) number categories between the mutation and non-mutation groups among all patients (P = 0.329) and 1292 patients (P = 0.408). Neither the 3-year DFS (97.9 % vs. 98.0 %, P = 0.832) nor the response to therapy distribution (P > 0.05) indicated a significant difference between the mutation and non-mutation groups. The 3-year DFS differs among patients having different LNM number categories (99.8 % vs. 98.5 % vs. 77.3 %, P < 0.001). Multivariate analysis revealed that high-volume (over 5) LNM (Total thyroidectomy (TT): OR = 4.000, 95 % CI 2.390-6.694, P < 0.001; Unilateral thyroidectomy (UT): OR = 4.183, 95 % CI 1.565-11.190, P = 0.004), rather than BRAFV600E mutation (P > 0.05), was an independent risk factor of response to therapy. CONCLUSIONS: Our results suggested that BRAFV600E mutation could not accurately predict LNM or the recurrence of Chinese PTMC patients. Moreover, high-volume LNM is significantly associated with PTMC prognosis.

A Long-Term Study Comparing the Quality of Life and Psychological Status of Patients with Highly Suspicious Thyroid Nodules ≤1 cm Undergoing Active Surveillance with Those Undergoing Immediate Surgery.

Background: Limited information is available on the long-term impact of active surveillance (AS) and immediate surgery (IS) on the quality of life (QoL) and psychological status of patients with highly suspicious subcentimeter thyroid nodules. Methods: A prospective study was conducted on 752 patients showing highly suspicious subcentimeter thyroid nodules, among whom 584 chose AS and 168 chose IS. All patients underwent at least two assessments regarding their QoL and psychological status, using three questionnaires: Thyroid Cancer-Specific Quality of Life (THYCA-QoL), Hospital Anxiety and Depression Scale (HADS), and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30). Propensity-score matching (PSM) at a ratio of 3:1 was utilized on patients in the AS and IS groups to mitigate selection bias (504 patients in the AS group and 168 in the IS group). Subsequently, the mixed linear model was used to analyze the QoL data. Results: The median time from the initial evaluation to the last follow-up in the AS and IS groups was 24.0 and 14.2 months, respectively. The AS group showed superior QoL outcomes compared to the IS group, mainly manifested in voice (p < 0.001), sympathetic (p = 0.008), throat/mouth (p < 0.001), and problems with scar (p < 0.001) domains, as per the THYCA-QoL questionnaire. Further, the EORTC QLQ-C30 questionnaire highlighted better outcomes in physical function (p = 0.029), role function (p < 0.001), social function (p < 0.001), global health status (p < 0.001), fatigue (p = 0.012), pain (p = 0.028), appetite loss (p = 0.017), and financial difficulties (p < 0.001). Compared to the initial assessment (1 week after surgery), the IS group showed progressive improvements in QoL, especially in voice (p = 0.024), throat/mouth (p < 0.001), physical function (p = 0.004), social function (p = 0.014), nausea and vomiting (p < 0.001), pain (p = 0.006), and appetite loss (p = 0.048) domains as per both questionnaires. Conclusion: Patients with highly suspicious subcentimeter thyroid nodules who choose IS tend to experience a poorer long-term QoL compared to those who choose AS. Although the situation may improve over time, certain issues might persist, making AS a favorable option for these patients.

FSCN1 has a potential indication for the prognosis and regulates the migration of HNSCC.

BACKGROUND: The study of molecular markers for diagnosis and prognosis is of great clinical significance for HNSCC patients. In this study, we proposed that FSCN1 has a potential indication for prognosis and is essential for the migration of HNSCC. METHODS: We analyzed the expression and survival association of FSCN1 in HNSCC using TCGA data. We compared the expression of FSCN1 in tumors from primary and metastasis HNSCC patients using QPCR, western blotting, and immunochemistry staining. We determined the migration velocity of multiple HNSCC cell lines using a chemotaxis migration assay. We analyzed the correlation between FSCN1 expression and HNSCC cell migration. We also test the effect of FSCN1 knockdown and overexpression on HNSCC cell migration. RESULTS: FSCN1 was overexpressed in HNSCC than pair normal tissues and metastasis HNSCC than primary HNSCC. FSCN1 expression was associated with significantly poorer overall survival of HNSCC patients. FSCN1 was potentially associated with immune cell infiltration and migration-associated genes. FSCN1 level was correlated with the migration in HNSCC cell lines. Knockdown of FSCN1 reduced the migration and the overexpression of FSCN1 promoted the migration of HNSCC cell lines. CONCLUSION: FSCN1 is a potential prognostic marker and a critical biomolecule for the migration of HNSCC.

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China.

INTRODUCTION: Active surveillance (AS) is considered an alternative to immediate surgery (IS) for low-risk papillary thyroid microcarcinoma (PTMC) patients. However, it is difficult to decide between AS and IS due to limited evidence regarding risks and benefits for patients in China. METHODS: This study prospectively enrolled 485 patients with highly suspicious thyroid nodules

The COVID-19 pandemic in various restriction policy scenarios based on the dynamic social contact rate.

The social contact rate has influenced the transmission of COVID-19, with more social contact resulting in more contagion cases. We chose 18 countries with the most confirmed cases in the first 200 days after the Wuhan lockdown. This was the first study using the dynamic social contact rate to simulate the epidemic under diverse restriction policies over 500 days since the COVID-19 outbreak. The developed General Dynamic Model suggested that the probability of contagion ranged from 12.52% to 39.39% in the epidemic. The geometric mean of the social contact rates differed from 18.21% to 96.00% between countries. The restriction policies in developed economies were 3.5 times more efficient than in developing economies. We compare the effectiveness of different policies for disease prevention and discuss the influence of policy adjustment frequency for each country. Maintaining the tightest restriction or alternate tightening and loosening restrictions was recommended, with each having an average 72.45% and 79.78% reduction in maximum active cases, respectively.

Active surveillance of highly suspicious thyroid nodules cohort in China shows a worse psychological status in younger patients.

Background: Active surveillance has been considered a safe alternative to surgery for low-risk papillary thyroid microcarcinoma. This study aimed to assess the oncological outcomes and psychological status of active surveillance of highly suspicious thyroid nodules ≤10 mm in China. Methods: This prospective single-center cohort study enrolled 336 patients with highly suspicious thyroid nodules for active surveillance to assess oncological outcomes and psychological status. The psychological status of patients was assessed by two different questionnaires and compared among different patient groups. Results: During a median follow-up period of 28.5 months, eight patients underwent delayed surgery for tumor enlargement and one for lymph node metastases. The cumulative incidence of disease progression at 5 and 10 years was 6.0% and 12.8%, respectively. Patients who underwent delayed surgery had no permanent complications, and no patient had distant metastasis or death. Patients ≤30 years old had a higher baseline anxiety score (4.9 vs. 3.8, p=0.024), a higher proportion of baseline anxiety score, i.e., ≥8 points (24.0% vs. 12.6%, p=0.033), and a worse baseline emotional function (62.7 vs. 70.7, p=0.013) than patients >30. During AS, patients ≤30 years of age had higher overall anxiety levels (p=0.005) and a worse overall emotional function (p=0.001). Conclusions: Active surveillance in Chinese patients with highly suspicious subcentimetre thyroid nodules has good oncological outcomes and can be used as a safe alternative to surgery. Younger patients (≤30) show a worse psychological status; therefore, more attention should be paid to younger patients.

c-Jun and Camk2a contribute to the drug resistance of induction docetaxel/cisplatin/5-fluorouracil in hypopharyngeal carcinoma.

Hypopharyngeal carcinoma (HPC) is a subtype of head and neck squamous cell carcinoma, and prognosis has improved significantly over the past three decades. Induction docetaxel/cisplatin/5 fluorouracil (TPF) chemotherapy is regarded as the standard of treatment for locoregionally advanced HPC. However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in TPF resistance and to clarify their molecular mechanisms. Using the FaDu cell line as the cell model, the TPF IC50 was identified, and c-Jun, IL6, Camk2a, c-fos knockdown using siRNAs resulted in a significant declined TPF IC50. Retrospective analysis of the expression status of c-Jun, IL6, Camk2a, and c-fos by immunohistochemistry staining in sectioned HPC tissues from TPF-sensitive and TPF-insensitive patients shows that Camk2a and c-Jun were associated with the clinical pathogenesic features in HPC. The in vitro experiments also indicate that both Camk2a and c-Jun were responsive to TPF treatment. This study identified Camk2a and c-Jun as candidate genes that confer induction TPF resistance, which would help in the discovery of potential therapeutic markers and in developing a personalized and precise treatment approach for HPC patients.

Rational choice of induction chemotherapy-based larynx preservation for hypopharyngeal cancer.

Backgroud: Induction chemotherapy, as a larynx preservation treatment, has been available for over 20 years. We conducted a retrospective study to evaluate the efficacy of this protocol with taxene, cisplatin and 5-fluorouracil in Chinese patients with hypopharyngeal cancer that chose preservation strategy. MATERIAL AND METHODS: 170 patients with locally advanced hypopharyngeal cancer were assigned to receive induction chemotherapy. 107 patients (63%) with complete response or partial response received larynx preservation treatment and 63 non-responders (37%) received radical surgery. RESULTS: Median survival time was 30 months (range: 3-59 months). 63 patients (37%) had local-regional failure and 15 (9%) had distant metastasis. Three-year LFS was 27.8% (95% CI: 23.6-32.0%). The estimated three-year overall survival rate was 44.5% (95% CI: 39.5-49.5%). There was no significant difference in the three-year survival rate between responders (44.8%) and non-responders (43.9%) (p = .237), however patients with a partial response had a significant decrease in survival (32.2%) (p < .001). CONCLUSIONS: In patients with hypopharyngeal cancer, ICT with TPF regimen followed by RT, as a larynx preservation treatment, may be suitable for complete responders, but not partial responders.

SLC7A11, a component of cysteine/glutamate transporter, is a novel biomarker for the diagnosis and prognosis in laryngeal squamous cell carcinoma.

Solute carrier family 7, membrane 11 (SLC7A11) or (xCT) is a component of the cysteine-glutamate transporter, which plays a critical role in glutathione homeostasis which is important to protect cells from oxidative stress. SLC7A11 is distributed in various tissues and participates in the occurrence of a number of diseases, particularly in the pathogenesis of malignant tumors, but its role in laryngeal cancer development has not yet been clearly defined. The objective of the present study was to investigate the role of SLC7A11 in laryngeal squamous cell carcinoma (LSCC). We conducted immunohistochemistry and RT-PCR to evaluate the protein and mRNA levels of SLC7A11 in LSCC and in control tissues, respectively. The knockdown experiments were conducted with SLC7A11 short hairpin RNA (shRNA) lentivirus, and the protein and mRNA levels of SLC7A11 were assessed by RT-PCR and western blotting. The functional study of SLC7A11 in vitro was conducted by MTT assay, and the effects on the cell cycle were detected using flow cytometry. Immunohistochemical results revealed that the expression levels of SLC7A11, Ki-67 and p53 in LSCC tissues were higher than those in laryngeal dysplasia tissues. The Spearman rank correlation analysis revealed that the expression of SLC7A11 was positively correlated with the expression of p53 and Ki-67. Cox regression analysis and Kaplan-Meier plots confirmed that the expression levels of SLC7A11 were a prognostic factor for overall survival (OS) rates and postoperative recurrence of LSCC. Moreover, the functional study of SLC7A11 in vitro revealed that knockdown of SLC7A11 using shRNA inhibited cell proliferation by inducing cell cycle arrest at the G1 phase. Immunohistochemical and RT-PCR results and knockdown experiments of SLC7A11 revealed that SLC7A11 was involved in the progression of LSCC, and may provide clinical information for the evaluation of OS rates and postoperative recurrence of LSCC. Collectively, these observations suggest that SLC7A11 may be a vital biomarker for the diagnosis and prognosis in human LSCC, and targeting SLC7A11 appears to be a potentially significant method for LSCC treatment.