Squamous Cell Carcinoma Antigen Research Articles

THE ROLE OF MOLECULAR DIAGNOSTICS AND BIOMARKERS IN TRANSFORMING CERVICAL CANCER MANAGEMENT

Cervical cancer is the fourth leading kind of cancer in women all over the world. More than 570,000 new cases and 311,000 deaths were registered in 2019, most in middle- and lower-income nations. The main reason is chronic infection with HPV infection, particularly types 16 and 18. Although the use of Pap smears and HPV testing has improved the survival rates, health inequities still allow high rates to be seen in many countries. A new development which comprises a short course of chemotherapy before chemo radiation is showing much promise, as it has reduced mortality rates by 40% and recurrence by 35%. Biochemical and hormonal markers are important in cervical cancer control. In understanding tumor advancement and the response to therapy, some markers like squamous cell carcinoma antigen (SCC-Ag) and lactate dehydrogenase (LDH) are relevant. Estrogen and progesterone receptors also affect tumor development, as the former exerts carcinogenic effects and the latter counters them, but the risk could potentially increase more in HPV-positive women due to hormonal contraceptives and changing levels at menopause. Some biochemical markers, like p16INK4a and Ki-67, as well as other inflammatory and metabolic markers, help in formulating individualized therapy. The process of detecting cervical cancer has changed because of the improvements brought about by NGS, liquid biopsy, and POCT. NGS makes it possible to devise an extensive report of the genome through Comprehensive Genomic Profiling. Liquid biopsy aids in observing and capturing cells in real time, while AI-powered POCT increases the accuracy of diagnosis in places where resources are scarce. These developments improve the metrics of outcome and healthcare delivery. To help resolve this avoidable illness, the WHOs goal of 90% immunization and screening by 2030 highlights the necessity for improved efforts in prevention, testing, and treatment.

A panel of cancer testis antigens in squamous cell carcinoma of the lung, head and neck, and esophagus: implication for biomarkers and therapeutic targets

This study aims to investigate the expression of seven cancer testis antigens (MAGE-A1, MAGE-A4, MAGE-A10, MAGE-A11, PRAME, NY-ESO-1 and KK-LC-1) in pan squamous cell carcinoma and their prognostic value, thus assessing the potential of these CTAs as immunotherapeutic targets. The protein expression of these CTAs was evaluated by immunohistochemistry in 60 lung squamous cell carcinoma (LUSC), 62 esophageal squamous cell carcinoma (ESCA) and 62 head and neck squamous cell carcinoma (HNSC). The relationship between CTAs expression and progression-free survival (PFS) was assessed. PD-L1 expression and tumor-infiltrating lymphocytes were also collected and correlated with CTAs expression. The prognostic impact of CTAs gene expression was evaluated using the Kaplan–Meier Plotter website. CTAs expression was 0–48% in ESCA, 3%-77% in LUSC, and 3%-71% in HNSC. Analysis of PFS showed that MAGE-A1 expression in HNSC (**p < 0.01), PRAME in LUSC (p = 0.008, **p < 0.01), MAGE-A10 (p = 0.012, *p < 0.05) and PRAME (p = 0.021, *p < 0.05) in ESCA were significantly correlated with PFS. In all three cancers, coexpression of three CTAs was used as a cutoff value for grouping, and the results showed a significant difference in PFS between these two groups. Moreover, CTAs expression was significantly correlated with PD-L1 expression and T cell infiltration. These findings indicate a high incidence of CTA expression in HNSC, LUSC and ESCA, which was correlated with PD-L1 expression, T cell infiltration, and tumor progression. The results suggest that cancer testis antigens could be feasible vaccine targets in squamous cell carcinoma.

Multi-center study on the application potential of Siaα-2,6Gal in early and differential diagnosis of lung cancer.

This study aimed to investigate the application potential of the abnormal glycan structure Siaα-2,6Gal in the early and differential diagnosis of lung cancer. Clinical data and serum samples from 730 patients and 120 healthy individuals participating in clinical trials on Siaα-2,6Gal were collected at three medical centers between January 2022 and June 2023. The levels of Siaα-2,6Gal, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (ProGRP) in serum were measured. The application potentials of these markers in the early and differential diagnosis, classification, and staging of lung cancer were explored. (1) Serum Siaα-2,6Gal levels in the lung cancer group were 2,606 (1,970-3,458) U/mL, significantly higher than those in the benign lung disease, miscellaneous malignant tumor, miscellaneous benign disease, and healthy individual groups at 1,359 (950-1,528), 1,252 (903-1,532), 1,196 (850-1,490), and 1,210 (1,100-1,287) U/mL (P < 0.0001). (2) Serum Siaα-2,6Gal levels in the early-stage lung cancer (stages 0-II) group were 2,576 (1,929-3,338) U/mL, significantly higher than those in the benign pulmonary nodule group at 1,419 (1,105-1,820) U/mL (P < 0.0001). (3) Receiver operating characteristic curves showed that Siaα-2,6Gal had a high diagnostic efficiency for lung cancer (area under the curve (AUC)=0.9217), significantly superior to CEA, CYFRA21-1, SCC, NSE, and ProGRP (AUCs of 0.6618, 0.6605, 0.5783, 0.5985, and 0.6381). Siaα-2,6Gal is a promising biomarker for lung cancer diagnosis and may offer superior differential diagnosis of early-stage lung cancer from benign pulmonary nodules compared to traditional tumor markers.

Predictive factors for failure of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy in esophageal squamous cell carcinoma.

Recently, neoadjuvant chemotherapy comprising docetaxel, cisplatin, and 5-fluorouracil showed promising efficacy for esophageal squamous cell carcinoma. However, some patients do not achieve curative resection despite neoadjuvant chemotherapy using these drugs. This study aimed to clarify the pretherapeutic characteristics of these patients. We included 113 patients who underwent neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for potentially resectable esophageal squamous cell carcinoma and compared the clinical characteristics between patients who achieved curative resection (curative group) and those who failed to achieve curative resection after planned neoadjuvant chemotherapy (noncurative group). Moreover, we determined the factors predicting noncurative outcomes. Ninety-one (81%) and 22 patients (19%) were in the curative and noncurative groups, respectively. The noncurative group had significantly more tumors located in the upper third of the esophagus, larger-sized tumors, and borderline resectable tumors than the curative group (P = 0.003, 0.049, and <0.001, respectively). Moreover, the noncurative group had significantly higher serum squamous cell carcinoma antigen concentrations than the curative group (P = 0.008). Multivariable analysis identified tumor location in the upper third of the esophagus (odds ratio 7.31, P = 0.002), tumor size ≥50mm (odds ratio 4.71, P = 0.037), and borderline resectable tumors (odds ratio 6.65, P = 0.003) as independent predictors for noncurative outcomes. Tumor location in the upper third of the esophagus, larger-sized tumors, and borderline resectable tumors might be significant predictors for noncurative outcomes in patients who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil.

Affinity Peptide-Based Circularly Permuted Fluorescent Protein Biosensors for Non-Small Cell Lung Cancer Diagnosis.

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and poses a significant public health challenge. Early detection is crucial for improving patient outcomes, with serum biomarkers such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCAg), and cytokeratin fragment 19 (CYFRA 21-1) playing a critical role in early screening and pathological classification of NSCLC. However, due to being mainly based on corresponding antibody binding reactions, existing detection technologies for these serum biomarkers have shortcomings such as complex operations, high false positive rates, and high costs. This study aimed to develop new methods for detecting CEA, SCCAg, and CYFRA 21-1 to assist in the diagnosis of NSCLC. Affinity peptides of CEA, SCCAg, and CYFRA 21-1, respectively, were screened by phage display technology, and the peptides' binding affinities were determined by enzyme-linked immunosorbent assay and biolayer interferometry. Peptides with high affinity were then integrated as binding domains into biosensors by fusing them with circularly permuted fluorescent proteins (cpFPs) through genetic coding. The resulting biosensors, C4 biosensor for CEA, S1 biosensor for SCCAg, and Y3 biosensor for CYFRA 21-1, demonstrated robust sensitivity and specificity even at concentrations as low as 1 ng/mL for their respective tumor markers. When applied to clinical samples and recalibrated for the upper limit of normal concentrations, the biosensors exhibited enhanced sensitivity and specificity for NSCLC diagnosis. This study introduced innovative biosensors for the detection of CEA, SCCAg, and CYFRA 21-1, providing a highly sensitive, specific, rapid, and cost-effective diagnostic alternative that could significantly improve NSCLC screening rates.

Diagnostic accuracy of folate receptor-positive circulating tumor cells in differentiating between benign and malignant pulmonary nodules.

Currently, traditional blood biomarkers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) etc. are mostly elevated in the late stage of tumour, and patients have already lost the chance of tumour eradication when the relevant indexes are found to be elevated. Therefore, there is a need for blood biomarkers with higher sensitivity, better specificity, and better accessibility. Folate receptor-positive circulating tumor cells (FR+CTCs) may have diagnostic value in lung cancer. Nevertheless, there is a scarcity of research exploring the efficacy of FR+CTCs in screening pulmonary nodules for lung cancer. The aims of this study were to differentiate between lung cancer and benign pulmonary nodules using FR+CTCs in conjunction with blood markers and to develop a composite diagnostic model for pulmonary nodules. Based on the inclusion and exclusion guidelines, we retrospectively analysed 1,135 patients with pulmonary nodules who underwent tissue biopsy or surgical resection after FR+CTC testing, assessed the histopathological findings by a specialised pathologist, and collected and compared demographic characteristics, blood markers, imaging and pathological parameters in malignant and benign patients. The random forest model was used to screen for indicators and to establish a composite index of blood biomarkers. The performance of single factors or the integrated model were estimated by applying receiver operating characteristic (ROC) analysis. A total of 612 patients were included in the lung cancer group, predominantly presenting with stage I adenocarcinomas (n=458). The median age was 54 years, and 43.1% of the patients were male. In comparison, 523 patients were included in the benign pulmonary nodules group, with a median age of 53 years and 46.8% male. No significant differences were identified between the two groups with regard to gender or age (P>0.05). The level of FR+CTCs in the lung cancer group was significantly higher than that in the benign nodule group (P<0.001). The white blood cell (WBC) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) levels were significantly higher in the lung cancer group than in the benign nodule group (P<0.001 and P=0.01, respectively). FR+CTC level was associated with the pathological subtype (P=0.02), WBC (P<0.001), and lactate dehydrogenase (LDH) level (P=0.01). In both groups, the FR+CTC level was higher in the single-nodule group than in the multiple-nodule group (P=0.002 and P=0.040, respectively). The diagnostic sensitivity and specificity of FR+CTCs for lung cancer at a cutoff of 8.7 FU/3 mL was 61.9% and 75.0%, respectively. Increasing the cutoff to 1.5 times (13.1 FU/3 mL) and 2 times (17.4 FU/3 mL) improved the specificity to 90.8% and 95.6%, respectively. The combination of FR+CTCs with WBC, procalcitonin, and LDH resulted in an area under the curve of 0.976 [95% confidence interval (CI): 0.910-1.000], a sensitivity of 100.0%, and a specificity of 85.7%. FR+CTC was proven to be a viable blood biomarker for aiding in the early detection of lung cancer. The combined model based on FR+CTC showed substantially greater accuracy than did any single biomarker in patients with pulmonary nodules.

Prognostic Impact of Squamous Cell Carcinoma Antigen During Neoadjuvant Chemotherapy for Patients With Esophageal Squamous Cell Carcinoma Treated With Minimally Invasive Esophagectomy.

Squamous cell carcinoma antigen (SCC) is widely used as a tumor marker for esophageal cancer. In this study, we investigated the relationship between SCC and long-term outcomes in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy (NAC) followed by minimally invasive esophagectomy (MIE). Between 2010 and 2018, 124 patients with ESCC who underwent MIE after NAC (cisplatin plus 5-fluorouracil) were included. Patients were divided into low and high groups based on their pre-NAC SCC level, according to the cut-off value determined using a receiver operating characteristic curve. These two patient groups were further divided into subgroups by receiver operating characteristics according to whether SCC was low or high after NAC. For overall survival (OS), the cut-off value for SCC pre-NAC was 0.9 ng/ml. Ninety-six patients were in the high SCC group (≥0.9 ng/ml) and 28 patients were in the low SCC group (<0.9 ng/ml) prior to NAC. The patients were then divided into pre-NAC/post-NAC SCC subgroups accordingly: low/low SCC (n=7), low/high SCC (n=21), high/low SCC (n=53), and high/high SCC (n=43). The 5-year OS rates were 100%, 66.7%, 50.9%, and 32.6%, respectively. In the multivariate analysis for OS, a high/high pre-NAC/post-NAC SCC status was an independent prognostic factor for poorer OS, along with pathological N stage. For patients with esophageal squamous cell carcinoma treated with NAC followed by MIE, a high SCC level prior to NAC which was also high after NAC was an independent prognostic factor and might contribute to deciding the need for adjuvant therapy.

Circulating Cell-free Human Papillomavirus DNA as a Tumor Marker in Recurrent or Metastatic Cervical Cancer: A Pilot Study

PURPOSE: Monitoring of circulating human papillomavirus (HPV) cell-free DNA (cfDNA) is a minimally invasive approach for surveillance in HPV-associated cancers, particularly cervical cancer. The aim of this study was to monitor circulating HPV cfDNA levels in patients with recurrent or metastatic cervical cancer during treatment and follow-up to assess the utility of HPV cfDNA as a tumor marker for disease surveillance and in guiding clinical treatment decisions. EXPERIMENTAL DESIGN: In this prospective pilot observational study, levels of HPV cfDNA in serum samples from 28 patients with recurrent or metastatic HPV+ cervical cancer were measured via digital droplet polymerase chain reaction. Results for HPV cfDNA levels were matched to clinical outcomes and to serum levels of squamous cell carcinoma antigen (SCC-Ag) to assess the clinical potential of HPV cfDNA as a tumor marker. RESULTS: HPV cfDNA was detected in all 28 patients (100%). Notably, median baseline HPV cfDNA levels varied according to the metastatic pattern in individual patients (P=0.019). Specifically, patients with a combined multiple-metastasis pattern had higher median baseline HPV cfDNA levels than patients with a single metastasis (P=0.003). All participants exhibited changes in HPV cfDNA levels over a median monitoring period of 2 months (range 0.3-16.9) before evaluations for treatment response or disease progression. Among 26 patients initially diagnosed with squamous cell cervical cancer, the positivity rate was 100% for HPV cfDNA and 69.2% for SCC-Ag (P=0.004, 95% confidence interval, 0-0.391). Among 20 patients longitudinally monitored for squamous cell cervical cancer, the concordance with changes in disease status was 90% for HPV cfDNA and 50% for SCC-Ag (P=0.014, 95% confidence interval, 0.022-0.621). CONCLUSIONS: HPV cfDNA is a promising tumor marker for HPV+ cervical cancer. In the context of precision medicine, HPV cfDNA is poised to play an increasingly pivotal role in monitoring treatment efficacy, providing valuable insights into disease progression, and guiding clinical decisions.

Evaluation of Amide Proton Transfer Imaging Combined With Serum Squamous Cell Carcinoma Antigen for Grading Cervical cancer.

The aim of the study is to investigate the efficacy of amide proton transfer-weighted (APT) imaging combined with serum squamous cell carcinoma antigen (SCC-Ag) in grading cervical cancer. Sixty-three patients with surgically confirmed cervical SCC were enrolled and categorized into 3 groups: highly differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3). The diagnostic efficacies of APT imaging and serum SCC-Ag, alone or in combination, for grading cervical SCC were compared. The APT values measured by the 2 observers were in excellent agreement (intraclass correlation coefficient >0.75). Mean (± standard deviation) APT values for the high, moderate, and poor differentiation groups were 2.542 ± 0.215% (95% confidence interval [CI]: 2.423-2.677), 2.784 ± 0.175% (95% CI: 2.701-2.856), and 3.120 ± 0.221% (95% CI: 2.950-3.250), respectively. APT values for groups G2 and G3 were significantly higher than those for G1 (P < 0.05). APT values for identifying cervical SCC in groups G1 and G2, G2 and G3, and G1 and G3, had areas under the receiver operating characteristic curve, sensitivities, and specificities of 0.815 (95% confidence interval [CI]: 0.674-0.914), 82.1%, and 72.2%, 0.882 (95% CI: 0.751-0.959), 70.6%, and 92.7%, and 0.961 (95% CI: 0.835-0.998), 94.1%, and 94.4%, respectively. APT values were significantly and positively correlated with the histological grade of cervical SCC (Spearman's correlation [rs] = 0.731, P < 0.01). Serum SCC-Ag levels for the high, moderate, and poor differentiation groups were 1.60 (0.88-4.63) ng/mL, 4.10 (1.85-6.98) ng/mL, and 26.10 (9.65-70.00) ng/mL, respectively. The differences were statistically significant only between groups G1 and G3 and G2 and G3 (P < 0.05), whereas the differences between groups G1 and G2 were not statistically significant (P > 0.05). Spearman's analysis revealed a positive correlation between SCC-Ag levels and the histological grade of cervical SCC (rs = 0.573, P < 0.01). The diagnostic efficacy of APT imaging for the histological grading of cervical SCC was better than that of serum SCC-Ag, and the discriminatory efficacy of the combination of the 2 parameters was better than that of either alone. The diagnostic efficacy of APT imaging was better than that of serum SCC-Ag, and the combined diagnostic utility of APT and SCC-Ag was better than that of the individual parameters.

Novel sensing signal mode constructed by dual responsive silence layer combined with catalytic hydrogen evolution

For electrochemical assays, to obtain sensing signals, the redox of the modified electrochemical signal substance to provide a detectable signal is commonly required. However, during the process of assembly and sensing, the loss of signal substance caused by multiple steps of modification, incubation, and washing would lead to non-negligible fluctuation of signal and lack of reproducibility. To overcome this issue, a novel sensing signal mode without electrochemical signal substance was developed. By introducing electrochemical catalytic hydrogen evolution into the sensing scheme, and taking the overpotential as the detectable signal, the sensing system was constructed in the absence of electrochemical signal substance. As a proof of concept, the sensor was used to quantify squamous cell carcinoma antigen, a model analyte, and exhibited an excellent analytical performance with a wide linear range from 0.100 ng mL−1 to 100 ng mL−1 and a low detection limit of 52.4 fg mL−1. As envisioned, the sensor exhibited excellent long-term stability and reproducibility due to the avoidance of signal substance. This method provided a new way for the design of electrochemical sensors.

Observations of the effectiveness, dosage, and prognosis of intensity-modulated radiation therapy under ultrasonic guidance for cervical cancer patients.

Volumetric modulated arc therapy (VMAT) guided by ultrasound is a novel radiation therapy technique that facilitates the delineation of the tumor target area under image guidance, enhancing the precision of radiation therapy and maximizing the protection of surrounding tissues. The objective of this paper is to investigate the effectiveness of VMAT under ultrasonic guidance for cervical cancer patients and its impact on radiotherapy dosage and prognosis. A retrospective analysis encompassed 128 instances of cervical cancer patients who were admitted to our medical facility between April 2019 and April 2021. The patients were categorized into an observation cohort and a control cohort, depending on variations in treatment modalities post-admission. The control group underwent conventional radiotherapy, whereas the observation group received VMAT guided by ultrasound. Clinical efficacy, average radiation dosages (in the radiotherapy target area, rectum, and bladder), radiotherapy-related toxicities during treatment, and one-year survival rates were compared between the two groups. Additionally, variances in pre- and post-treatment serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 724 (CA724) were subjected to assessment. When compared to the control group (64.52%), the observation cohort's comprehensive effectiveness rate was considerably greater (80.30%). The observation group saw lower average radiation exposures and a reduction in the post-treatment concentrations of CEA, SCC-Ag, and CA724. The overall incidence of adverse effects from radiation treatment also declined. The observation group had a greater one-year survival rate (90.48%) than the control group (73.33%). When comparing the observation cohort to the control group, Kaplan-Meier survival analysis showed a significantly higher one-year survival rate (Log-Rank = 6.530, P= 0.011). VMAT guided by ultrasound for patients with cervical cancer demonstrates promising short- and long-term treatment outcomes. It also leads to improvements in serum CEA, SCC-Ag, and CA724 levels, as well as reductions in the average radiation dosages to the radiotherapy target area, rectum, and bladder. This approach warrants attention from clinicians in clinical practice.

Prediction of preoperative lymph-vascular space invasion and survival outcomes of cervical squamous cell carcinoma by utilizing 18 F-FDG PET/CT imaging at early stage.

To establish nomograms for predicting preoperative lymph-vascular space invasion (LVSI) and survival outcomes of cervical squamous cell carcinoma (CSCC) based on PET/CT radiomics. One hundred and twenty-three patients with CSCC and LVSI status were enrolled retrospectively. Independent predictors of LVSI were identified through clinicopathological factors and PET/CT metabolic parameters. We extracted 1316 features from PET and CT volume of interest, respectively. Additionally, four models (PET-RS: radiomic signature of PET only; CT-RS: radiomic signature of CT only; PET/CT-RS + clinical data; PET/CT-RS: radiomic signature of PET and CT) were established to predict LVSI status. Calculation of radiomics scores of PET/CT was executed for assessment of the survival outcomes, followed by development of nomograms with radiomics (NR) or without radiomics (NWR). One hundred and twenty-three patients with pathologically confirmed CSCC had been categorized into two sets (training and testing sets). It was found that only maximum standardized uptake value (SUV max ) and squamous cell carcinoma antigen were independent predictors of LVSI. Meanwhile, the PET/CT-RS + clinical data outperformed the other three models in the training set [area under the curve (AUC): 0.91 vs. 0.861 vs. 0.81 vs. 0.814] and the testing set (AUC: 0.885 vs. 0.857 vs. 0.783 vs. 0.798). Additionally, SUV max and LVSI had been demonstrated to be independent prognostic indicators for progression-free survival and overall survival. Decision curve analysis and calibration curve indicated that NRs were superior to NWRs. The survival outcomes were assessed. PET/CT-based radiomic signature nomogram enables a new method for preoperative prediction of LVSI and survival prognosis for patients with CSCC.

Development and validation of a tumor marker-based model for the prediction of lung cancer: an analysis of a multicenter retrospective study in Shanghai, China.

The incidence and mortality rates of cancer are the highest globally. Developing novel methodologies that precisely, safely, and economically differentiate between benign and malignant lung conditions holds immense clinical importance. This research seeks to construct a predictive model utilizing a combination of diverse biomarkers to effectively discriminate between benign and malignant lung diseases. This retrospective study included patients admitted to the two general hospitals in Shanghai from 2014 to 2015. This study was developed using five tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), cytokeratin fragment 21-1 (CA211), squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE). The entire sample was divided into two groups according to the hospital: 1033 cases were included in the development cohort and 300 cases in the validation cohort. Logistic regression analysis was used for univariate analysis to explore individual correlations between each selected clinical variable and lung cancer diagnostic outcome. Diagnostic prediction models were constructed and validated based on independent prognostic factors identified using multifactorial analysis. A nomogram was created using these tumor markers (age and sex were additionally included) and validated using the concordance index and calibration curves. Clinical prediction models were evaluated using decision curve analysis. Fully adjusted multivariate analysis showed that the risk of lung cancer was 2.38 times higher in men than in women. CEA positivity was associated with an 13.41-fold increased risk in lung cancer. The area under the curve (AUC) values for the development cohort and validation cohort models were 0.907 and 0.954, respectively. In the established nomogram, the AUC for the receiver operating characteristic curve was 0.907 (95% CI, 0.889-0.925). The validation model confirmed the strong discriminative power of the nomogram (AUC = 0.954). The described calibration curves demonstrated good fit predictions and observation probabilities. In addition, decision curve analysis concluded that the newly established nomogram has important implications for clinical decision making. Combined prediction models based on CEA, CA199, CA211, SCC, and NSE biomarkers could significantly the differentiation between benign and malignant lung diseases, thus facilitating better clinical decision making.

Detection of Protein Markers From Blood Samples of Cervical Cancer Patients.

Objective Human papillomavirus (HPV) is the prevalent cause of cervical cancer in females worldwide, necessitating the development of fast and reliable diagnostic methods for early detection of HPV. The study aims to detect serum proteins like squamous cell carcinoma antigen (SCCA/SerpinB3), cytokeratin fragment antigen 21-1 (CYFRA 21-1), carcinoembryonic antigen (CEA), and high mobility group box chromosomal protein 1 (HMGB1) as biomarkers and their combination concerning the type of HPV. Methods Serum samples from a total of 36 cervical cancer patients were initially subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by western blotting with anti-Serpin B3/SCCA, anti-CEA, anti-HMGB, and anti-CYFRA 21-1.The frequency of samples for each protein was obtained. In the Chi-square test, correlations with p-values less than 0.05 were deemed statistically significant. Results Irrespective of HPV type, the CEA had the highest percentage of definite responses (58.33%). Subsequently, SCCA, HMGB1, and Cytokeratin-19 protein presented 47.22%, 27.78%, and 25% responses, respectively. HPV types influenced thedifference inprotein combinations, with HPV-16 presenting the most positive responses followed by HPV-(16+18). HPV-18 presented the least number of affirmative responses. Conclusion Our study presents the CEA protein as a possible biomarker and HPV-16 as the most prominent HPV type to different parallel combinations of serum proteins. The protein combinations canbe appliedto future cancer detection and therapy.

Fast tailoring the ZIF-8 surface microenvironment at ambient temperature to boost glucose oxidase-like activity of AuNPs for biosensing

Rational design and tailoring of the surface microenvironment surrounding the catalytic sites, such as noble metal nanoparticles, is an effective way to enhance the catalytic activity of mimicking enzymes. However, it remains on-going challenges to regulate the microenvironment of the catalytic sites due to the lack of tunable variability in structural precision of conventional solid catalysts. Herein, three types of zeolitic imidazolate framework-8 (ZIF-8) with different major crystal facet orientations, i.e., cubic with (100) facets (denoted ZIF-8c), truncated dodecahedral with (100), (110) facets (denoted ZIF-8tr), and dodecahedral with (110) facets (denoted ZIF-8r), were developed facilely using an electrochemical method by switching the potential at ambient temperature. Because the Zn2+ nodes were predominantly exposed on the (100) facets of ZIF-8, while the ligands were mainly exposed on the (110) facets. Hence, gold nanoparticles (AuNPs) showed differential glucose oxidase (GOx)-like activities when anchored in situ on different crystal facets of ZIF-8 and obeyed the following order ZIF-8c/Au>ZIF-8tr/Au>ZIF-8r/Au. Notably, both the metal nodes and aromatic linkers of ZIF-8 interacted with AuNPs through coordination and π-π interactions. The Zn2+ nodes facilitated the formation of the electron-deficient Au species. The electron transfer from AuNPs to Zn2+ sites effectively boosted the catalytic activity. It was known that directly tailoring the microenvironment at the supporting sites of noble metal catalysts to boost catalysis through a facile electrochemical method was not reported. Based on the favorable GOx-like activity and long-term stability of ZIF-8tr/Au, a highly sensitive electrochemical biosensing platform for assaying squamous cell carcinoma antigen (SCCA) was developed. It enabled fg-level detection of cancer marker.

Efficacy of total laparoscopic hysterectomy without uterine manipulators in patient with early-stage cervical cancer.

To evaluate the feasibility and safety of total laparoscopic hysterectomy (TLH) without uterine manipulator for patients with early-stage cervical cancer. This study was based on retrospective analysis of clinical data of 72 patients with early-stage cervical cancer who received TLH treatment in Meizhou People's Hospital from January 2018 to December 2020. Of them, 40 patients underwent routine TLH (control group), and 32 patients received TLH without lifting the uterus using uterine manipulator (observation group). Changes in tumor marker levels, human papilloma virus (HPV) status, complications, and survival between two groups of patients were compared. There was no significant difference in the incidence of postoperative complications between the two groups (P>0.05). After the surgery, levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA-125) in both groups of patients were significantly reduced compared to before the surgery, and significantly lower in the observation group compared to the control group at one and two years after the surgery (P<0.05). After three years of postoperative follow-up, there was no significant difference in cumulative survival rates between the two groups (P>0.05). Compared with conventional laparoscopy, hysteroscopy without the use of uterine manipulators can significantly reduce the levels of SCC-Ag, CEA, and CA-125 in patients with early-stage cervical cancer within two years after the surgery, without increasing postoperative complications or affecting survival, and has the same safety.

Roles of microRNA-486-5p in the diagnosis and the association with clinical symptoms of cervical cancer.

Aim: To explore the predictive value of miR-486-5p in early cervical cancer and the associations of miR-486-5p with different clinical symptoms.Materials & methods: A total of 185 women were recruited. The relative expression levels of serum miR-486-5p were analyzed by real-time polymerase chain reaction. The receiver operator characteristic curves were utilized to reflect the predictive performance of miR-486-5p and squamous cell carcinoma antigen for early cervical cancer. Univariate logistic regression and ranked logistic regression were used to explore the associations of miR-486-5p with different clinical symptoms of early cervical cancer, with odd ratios (ORs) and 95% confidence intervals.Results: Eighty-one women (44.26%) had early cervical cancer. The relative expression of serum miR-486-5p was 1.99-fold higher in early cervical cancer patients than that in controls (p<0.0001). The predictive performance of miR-486-5p for early cervical cancer was significantly superior to that of squamous cell carcinoma antigen, with an area under the curve of 0.865 (p<0.001), sensitivity of 1.000and specificity of 0.804. In addition, overexpressed miR-486-5p was associated with high odds of maximum tumor diameter increase (OR=1.30, 95%CI: [1.01-1.66]).Conclusion: MiR-486-5p may be a potential biomarker for the early cervical cancer diagnosis, and was linked to the risk of maximum tumor diameter.

Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

Preoperative scoring system for the prediction of risk of lymph node metastasis in cervical cancer

The study aimed to develop and validate a preoperative scoring system to predict the risk of lymph node metastasis (LNM) in cervical cancer (CC). A total of 426 stage IB1–IIA1 CC patients were randomly divided into two sets. A logistic regression model was used to determine independent factors that contribute to LNM. A preoperative scoring system was developed based on beta (β) coefficients. An area under the receiver operating curve (AUC) was used to test for model discrimination. Five-year overall survival (OS) rate was 91.7%. Multivariable logistic regression analysis showed that FIGO stage, tumor size, depth of invasion on MRI, and squamous cell carcinoma antigen levels were independent risk factors in the development set (all P < 0.05). The AUCs of the scoring system for the development and validation sets were 0.833 (95% CI = 0.757–0.909) and 0.767 (95% CI = 0.634–0.891), respectively. Patients who scored 0–2, 3–5, and 6–8 were classified into low-risk, medium-risk, and high-risk groups. Predicted rates were in accord with observed rates in both sets. The 5-year OS rates of the new groups were also significantly different for the entire group, development set, and validation set (all P < 0.05). LNM affects the prognosis of CC patients. The scoring system can be used to assist in evaluating the risk of LNM in CC patients preoperatively. It is easy to obtain and can provide reference for clinical treatment decision-making.

The treatment response evaluation through the combination of contrast-enhanced ultrasound and squamous cell carcinoma antigen in cervical cancer.

The evaluation of the treatment response after concurrent chemotherapy and radiotherapy (CCRT) for locally advanced cervical cancer is closely related to the formulation of treatment strategies. Magnetic resonance imaging (MRI) is a recommended method for efficacy evaluation; however, a unified consensus has not yet been reached on its use, and it has its limitations. This study aimed to evaluate the diagnostic value of a combination of contrast-enhanced ultrasound (CEUS) parameters and the squamous cell carcinoma antigen (SCC-Ag) to establish another efficient and feasible examination method. The data of 94 patients with cervical cancer who underwent transvaginal contrast-enhanced ultrasound (TV-CEUS) from October 2020 to March 2023 were retrospectively collected. Based on the inclusion and exclusion criteria, 70 patients diagnosed with cervical squamous cell carcinoma (SCC) who underwent CCRT were selected for inclusion in the study. The patients were divided into the residual disease (RD) group (comprising 26 patients) and the complete response (CR) group (comprising 44 patients) according to the diagnostic standard. Data on the grayscale echogenicity, color Doppler flow imaging (CDFI), CEUS parameters, and the SCC-Ag of all the patients were collected by two experienced radiologists. Inter-observer reliability was assessed using the intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were created based on the non-parametric U-test or t-test results for the two groups. Delong's test was used to compare the area under the curve (AUC) between different ROC curves. A subgroup analysis was conducted based on the patient's age, tumor diameter, and disease stage. The ICCs between the two observers ranged from 0.915 and 0.947. Hypervascular hyper-enhancement in the arterial phase, hypo-enhancement in the venous phase, and the SCC-Ag differed significantly between the RD and CR groups (P<0.05). The AUC of the ROC curve combining these indicators was 0.890 [95% confidence interval (CI): 0.792-0.989], which was higher than the AUC of any indicator alone (P<0.05). The subgroup analysis showed that the AUCs of the patients aged ≥53 and <53 years were 0.922 (95% CI: 0.816-1.00) and 0.896 (95% CI: 0.782-1.00), respectively, those of the patients with stage II, III, and IV were 0.881 (95% CI: 0.732-1.00), 0.955 (95% CI: 0.894-1.00), and 1.000 (95% CI: 1.00-1.00), respectively, and those of the patients with a tumor diameter ≤10 mm, 10 mm < tumor diameter (post) <20 mm, and tumor diameter (post) ≥20 mm were 0.976 (95% CI: 0.910-1.00), 0.883 (95% CI: 0.763-1.00), and 1.00 (95% CI: 1.00-1.00) respectively. Transvaginal ultrasound (TVUS), TV-CEUS, and the SCC-Ag can be used in combination to evaluate the patient response to CCRT in locally advanced cervical SCC. This integrated approach enhanced the accuracy of the diagnosis of residual lesions and may be helpful in treatment plan optimization.