Squamous Cell Carcinoma Antigen Research Articles

Nomograms to predict tumor regression grade (TRG) and ypTNM staging in patients with locally advanced esophageal cancer receiving neoadjuvant therapy

BackgroundNeoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult.MethodsA retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors.ResultsA total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility.ConclusionThe nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.

Prognostic value of HPV circulating tumor DNA detection and quantification in locally advanced cervical cancer.

Cervical cancers are mainly caused by an oncogenic HPV. For locally advanced stages, the standard treatment is radio-chemotherapy (RTCT) followed by brachytherapy. Nevertheless, the prognosis remains highly heterogeneous between patients. We investigated the prognostic value of HPV circulating tumor DNA (ctDNA) in locally advanced cervical cancers alongside that of Squamous Cell Carcinoma Antigen (SCC-A). This single-center retrospective study included patients treated in curative intent for an IB3 to IVA squamous cell cervical cancer. Quantification of HPV ctDNA in serum collected at diagnosis was performed using a multiplex digital PCR assay for the simultaneous detection of 8 HPV genotypes. Among the 97 patients included, 76 patients (78.4%) were treated by RTCT, followed by brachytherapy for 57 patients (60%). HPV ctDNA was detected in 59/97 patients at diagnosis (60.8%). This detection was associated with lymph node invasion (p=0.04) but not with tumor stage. A high level of SCC-A at diagnosis was associated with tumor stage (p=0.008) and lymph node invasion (p=0.012). In univariate analysis, better disease-free survival (DFS) was associated with optimal RTCT regimen (p=0.002), exposure to brachytherapy (p=0.0001) and a low SCC-A at diagnosis (continuous analysis, p=0.002). Exploratory analysis revealed that 3/3 patients (100%) whose HPV ctDNA was still detectable at the end of treatment relapsed, while 6/22 patients (27.3%) whose HPV ctDNA was negative at the end of treatment relapsed. HPV ctDNA detection at diagnosis of locally advanced cervical squamous cell carcinomas is frequent and related to node invasion, but not to DFS. The prognostic value of HPV ctDNA detection after treatment warrants specific studies.

Role of squamous cell carcinoma antigen (SCC-Ag) in the management of carcinoma cervix in an Indian population: A pilot study

BackgroundEarly detection of recurrence in carcinoma cervix can be challenging but has the potential to improve survival in a subset of patients. Squamous cell carcinoma antigen (SCC-Ag) has been tested in multiple roles in the management of cervical cancer but the evidence from India is limited. MethodsThis was a prospective, cohort pilot study conducted in a tertiary care hospital in central India. Study subjects were patients with locally advanced carcinoma cervix treated with concurrent chemoradiotherapy between June 2017 and May 2018. All patients underwent pre and post-treatment SCC-Ag testing which was continued serially every 3 months for a total follow-up of 24 months. A cut-off value of 1.5 ng/ml or more was used to define a positive test. Chi–Square tests, Pearson's correlation testing and Kaplan Meier plots were used to study the association of different patient and tumour variables with the SCC-Ag levels. Test validity of serial measurements of SCC-Ag was also measured for detection of recurrence. ResultsA total of 45 patients were included. SCC-Ag levels were strongly correlated with tumour stage and presence of lymph nodal metastases. Post-treatment abnormal SCC-Ag levels were significantly associated with a poorer recurrence-free survival (RFS). Serial measurement of SCC-Ag levels proved to be a good screening tool for early detection of recurrences even before clinical symptoms or signs developed with a sensitivity of 90% and specificity of 91.8%. ConclusionOur study has highlighted the benefits of the use of this tumour marker in the management of cervical cancer and has generated useful evidence supporting its use in prognosticating patients, guiding investigations, determining risk for recurrence, assessing tumour response and for early detection of recurrences.

Effects of Sintilimab Plus Radiotherapy on Levels of Spondin-2 and Glucose Transporter-1 in Patients with Cervical Cancer.

We aimed to evaluate the effects of sintilimab plus radiotherapy on levels of Spondin-2 and glucose transporter-1 (Glut-1) in patients with cervical cancer. A total of 112 patients with cervical cancer treated from January 2019 to January 2021 were selected in this randomized control trial and divided into a control group (n = 56) and a study group (n = 56) using the random number table method. Chemotherapy using docetaxel + cisplatin was performed for both groups, based on which the control group was given radiotherapy (external conformal radiotherapy + intracavitary irradiation), and the study group received sintilimab plus radiotherapy. The treatment lasted for six cycles, with 21 days as one cycle. The total response rate of the study group was higher than that of the control group (55.36% vs 33.93%) (P < 0.05). There were no significant differences in adverse effects between the two groups (P > 0.05). After six cycles of treatment, the levels of carcinoembryonic antigen, squamous cell carcinoma antigen, vascular endothelial growth factor-A, vascular endothelial growth factor receptor 2, Spondin-2 and Glut-1 decreased in both groups compared with those before treatment, and they were lower in the study group (P < 0.05). The survival rate of the study group was higher than that of the control group (87.50% vs 71.43%) (P < 0.05). Sintilimab plus radiotherapy can effectively reduce the levels of serum tumor markers, such as Spondin-2 and Glut-1, and enhance the clinical efficacy on patients with cervical cancer, without increasing adverse effects.

Effectiveness Analysis of the Combined Detection of CEA, SCC, CYFRA21-1, NSE and ProGRP for Early Diagnosis of Lung Cancer

Objective To explore the diagnostic value and application effect of the combined detection of CEA (carcinoembryonic antigen), SCC (squamous cell carcinoma antigen), CYFRA21-1 (soluble fragment of cytokeratin 19), NSE (neuron specific enolase) and proGRP (gastrin releasing peptide precursor) in early lung cancer. Method 66 patients who admitted to the hospital from April 2019 to February 2024 were selected as the early stage lung cancer group and the other 159 patients were selected as the benign lung group, in which all subjects were tested for NSE, CEA, ProGRP, CYFRA21-1, and SCC levels and were confirmed by histopathological analysis. In ROC analysis, the cut-off point, AUC, accuracy, sensitivity and specificity between single and combined detection indicators are analyzed. Result The size of cut-off point, AUC, accuracy, sensitivity, specificity, positive and negative detection rate and accuracy rate is 0.3072, 0.790, 89.33%, 0.894, 0.893, 89.40% (59/66), 89.31% (142/159) and 89.33% ((142+59)/225) respectively and it is obviously superior to those of single detection method. Meanwhile, indicator of SCC showed the worst performance by single detection. Conclusion The combined detection indicators have high diagnostic value in early diagnosis of lung cancer, and the sensitivity, positive detection rate, AUC value and accuracy have been significantly improved.

Diagnostic value of serum squamous cell carcinoma antigen and cytokeratin fragment antigen 21-1 for sinonasal inverted papilloma: an exploratory study.

Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP. Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified. Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767. This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

Interaction between RNF4 and SART3 is associated with the risk of schizophrenia

The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.

The value of plasma omega-3 polyunsaturated fatty acids in predicting the response and prognosis of cervical squamous cell carcinoma patients to concurrent chemoradiotherapy.

Background: In recent years, abnormalities in plasma omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been proven to be related to the risk of cancer, but their prognostic value for cancer is unclear. The purpose of this study was to retrospectively evaluate the response and prognostic significance of plasma omega-3 PUFAs in patients with cervical squamous cell carcinoma (CSCC) treated with concurrent chemoradiotherapy (CCRT). Spearman rank correlation analysis was used to analyze the correlation between omega-3 PUFAs and squamous cell carcinoma antigen (SCC-Ag) levels. Methods: A total of 89 patients with CSCC who underwent CCRT were evaluated retrospectively. Binary logistic regression analysis was used to analyze the independent predictors related to complete response (CR) after CCRT. A Cox proportional hazard model and Kaplan-Meier analysis were utilized to perform survival analysis. Results: According to multivariate logistic regression analyses, a high level of plasma EPA was independently correlated with an increased incidence of CR after CCRT (odds ratio (OR), 0.980; 95% confidence interval (CI), 0.962-0.999, p = 0.038). With a median follow-up of 41.3months, the CSCC patients in the high EPA (≥46.0nmol/mL) group exhibited longer OS and PFS. According to our multivariate analysis, pretreatment plasma EPA level was an independent prognostic factor for PFS in patients with CSCC who underwent CCRT (hazard ratio (HR), 0.263; 95% CI, 0.089-0.782, p = 0.016). However, it was not an independent prognostic factor of OS. Spearman rank correlation analysis revealed was a negative correlation between pretreatment SCC-Ag (pre SCC-Ag) levels and EPA levels (r = -0.305, p = 0.004), and a weak negative correlation between posttreatment SCC-Ag (post SCC-Ag) levels and EPA levels (r = -0.251, p = 0.018). Conclusion: Plasma omega-3 PUFAs are related to the response and survival outcome of patients with CSCC who underwent CCRT. Pretreatment plasma EPA levels may be a promising biomarker for predicting the response and prognosis of patients with CSCC who undergo CCRT. In addition, the pretreatment plasma EPA levels presented a negative correlation with the SCC-Ag levels.

Prospective Analysis of Squamous Cell Carcinoma Antigen-1 and -2 for Diagnosing Sinonasal Inverted Papilloma.

Background: The goal of this research was to confirm whether preoperative serum squamous cell carcinoma antigen (SCCA)-1 and -2 levels are useful diagnostic markers for sinonasal inverted papilloma (IP) in a prospective study. Methods: Participants were 102 patients who underwent consecutive endoscopic sinus surgery: 18 with IP, two with other types of papilloma, 77 with chronic rhinosinusitis, four with sinonasal cancer, and one with hemangioma. SCCA-1 and SCCA-2 were measured preoperatively by an automatic chemiluminescence immunoassay and an enzyme-linked immunosorbent assay, respectively. Results: SCCA-1 and SCCA-2 values were significantly correlated (r = 0.603, p < 0.001). Receiver operating characteristic analysis for differentiating papilloma (IP and other types of papilloma) from other diseases yielded an area under the curve of 0.860, with a Youden index of 1.75. Combined with SCCA-2 analysis, the detection system had a sensitivity and specificity of 0.65 and 0.98, respectively. While our study did not find a strong link between SCCA levels and skin or lung diseases, smoking status may influence SCCA levels in IP patients (p = 0.035). We recommend a cutoff value of 1.8 ng/mL for SCCA-1 in IP diagnosis. Conclusions: SCCA-1 and SCCA-2 when combined with imaging and pathology hold promise for enhancing the preoperative detection of IP, which would be a valuable contribution to clinical practice.

Determination of the cervical cancer biomarker SCCA using CMK-3@UiO-66@AuNPs composite-modified glassy carbon electrodes

In order to detect the cervical cancer biomarker squamous cell carcinoma antigen (SCCA) in human serum, an electrochemical immunosensor was constructed. Zirconium 1,4-dicarboxybenzene MOF (UiO-66), with a high specific surface area, was coupled with gold nanoparticles (AuNPs), creating the UiO-66@AuNPs nanomaterial. This coupling increased the sensitivity of the electrochemical immunosensor by providing many biological binding sites for antibodies to bind to Au-S bonds. Then, mesoporous carbon (CMK-3) was added to the UiO-66@AuNPs nanomaterial to obtain a CMK-3@UiO-66@AuNPs nanocomposite. This further increased the electron transfer proficiency of the material and enhanced the electrochemical signal. Finally, the sensitive detection of squamous cell carcinoma antigen (SCCA) was made possible by unique immunological responses between antigens and antibodies. Transmission electron microscopy (TEM) analysis of CMK-3@UiO-66@AuNPs revealed embedded surfaces and voids; cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) confirmed the successful assembly of the electrochemical immunosensor. The developed electrochemical immunosensor demonstrated good linearity (R12 = 0.999) from 0.01 pg/mL to 10,000 pg/mL, which is the concentration range of SCCA in human serum. The limit of detection was 0.0034 pg/mL (at an S/N ratio of 3). The immunosensor exhibited excellent precision, stability and selectivity, with a high rate of recovery (98.26–101.8 %). The experimental validation studies demonstrated that the electrochemical immunosensor was effective for the detection of SCCA in human serum, offering a novel method for the early diagnosis and dynamic surveillance of cervical cancer.

209: Squamous cell carcinoma antigen and its log change after radiotherapy in cervical cancer

209: Squamous cell carcinoma antigen and its log change after radiotherapy in cervical cancer

Accuracy of surveillance serum squamous cell carcinoma antigen for cervical cancer recurrence after definitive chemoradiation

ObjectiveRecurrence remains a significant clinical problem for patients with cervical cancer, and early detection may improve outcomes. Serum squamous cell carcinoma antigen (SCCA) is a biomarker of prognosis and response...

Clinical Significance of Serum SCC Levels Before Treatment for Locally Advanced Cervical Squamous Cell Carcinoma.

Although serum squamous cell carcinoma (SCC) antigen values are known to be useful in predicting the prognosis of cervical SCC, they have only been examined in a cursory manner. This study aimed to meticulously investigate the clinical significance of serum SCC antigen levels in patients with locally advanced cervical squamous cell carcinoma (LACSC). The study included patients who were diagnosed with local stage (T-stage) 1b3/2/3 LACSC and underwent initial treatment at our institute between January 2006 and December 2016 (T-1b3: n=30; T-2: n=75; T-3: n=34). The patients were divided into three groups based on pre-treatment SCC values, and differences in clinical background, laboratory and pathology findings, and prognosis were examined. No significant difference in the SCC distribution was observed among the T-1b3/2/3 cases with elevated SCC levels. In stages T-1b3, T-2, and T-3, most recurrences in the SCC-High group were distant (T-1b3: three out of five recurrences; T-2: six out of seven recurrences; T-3: four out of eight recurrences), while most recurrences in the SCC-Low group were pelvic (T-1b3: two out of three recurrences; T-2: eight out of eight recurrences; T-3: three out of three recurrences). In LACSC, serum SCC antigen levels before treatment correlate strongly with the recurrence site. Patients with low levels should be closely monitored for local recurrence, whereas those with high levels warrant vigilance for distant recurrence.

Prognostic analysis of stage IIIC1p cervical cancer patients.

Stage IIIC1p cervical cancer is characterized by marked heterogeneity and considerable variability in the postoperative prognosis. This study aimed to identify the clinical and pathological characteristics affecting the survival of patients diagnosed with stage IIIC1p cervical cancer. We retrospectively analyzed patients diagnosed with stage IIIC1p cervical cancer who underwent radical hysterectomy and lymph node dissection between March 2012 and March 2022. Overall survival (OS) was estimated using Kaplan-Meier survival curves. Univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors for OS and forest plots were used to visualize these findings. Nomogram charts were created to forecast survival rates at 3 and 5 years, and the accuracy of predictions was evaluated using Harrell's concordance index (C-index) and calibration curves. The study cohort comprised 186 women diagnosed with stage IIIC1p cervical cancer. The median follow-up duration was 51.1 months (range, 30-91 months), and the estimated 5-year OS rate was 71.5%. Multivariate analysis revealed that concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT + AC), monocyte-lymphocyte ratio (MLR), ratio of lymph node metastasis (LNM), and squamous cell carcinoma antigen (SCCA) levels independently predicted OS. Significant prognostic disparities exist among patients diagnosed with stage IIIC1p cervical cancer. MLR, ratio of LNM, and SCCA were associated with poor OS. In contrast, the CCRT + AC treatment regimen appeared to confer a survival advantage.

Average log change rate of pretreatment squamous cell carcinoma antigen after concurrent chemoradiotherapy in stage IIIC1 cervical squamous cell carcinoma

We aimed to determine whether pretreatment squamous cell carcinoma antigen (SCC-Ag) levels and the average logarithmic change in SCC-Ag levels (ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document}) after concurrent chemoradiotherapy (CCRT) could predict treatment outcomes in patients with stage IIIC1 cervical squamous cell carcinoma (SCC). We analyzed 168 patients with stage IIIC1 cervical SCC who underwent primary CCRT and collected data on age, local extension, treatment details, hematological parameters, and tumor markers such as SCC-Ag and carcinoembryonic antigen 21-1 (Cyfra). Predictive performances of pretreatment SCC-Ag levels and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} were assessed using receiver operating characteristic curves. Survival analysis was performed using the Cox regression model and Kaplan–Meier plots. The combination of pretreatment SCC-Ag levels and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} showed higher area under the curve values than pretreatment SCC-Ag levels alone (area under the curve; 95% confidence interval [CI] 0.708 [0.581–0.836] vs. 0.666 [0.528–0.804], respectively). Pretreatment SCC-Ag (≥ 5 ng/ml and Cyfra levels (≥ 3.15 ng/ml) and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} (≥ − 1.575) were significant predictors of disease-specific survival. The 5-year disease-specific survival rates significantly differed among the low-, intermediate-, and high-risk groups. Risk stratification using both pretreatment SCC-Ag levels and ΔlogSCC-AgΔtime\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{{\\Delta \\log \\left( {{\ ext{SCC-Ag}}} \\right)}}{{\\Delta {\ ext{time}}}}$$\\end{document} may predict treatment outcomes of patients with stage IIIC1 SCC.

Human epididymal protein 4 and its combined detection show good diagnostic value in lung cancer: A retrospective study.

This study aimed to assess the diagnostic value of human epididymal protein 4 (HE4), a potential novel biomarker for lung cancer, and its combined detection with five other conventional biomarkers in lung cancer diagnosis and subtyping. In this retrospective study, 115 lung cancer patients, 50 patients with benign pulmonary disease, and 50 healthy controls were included. Serum HE4, progastrin-releasing peptide (ProGRP), squamous cell carcinoma (SCC) antigen, cytokeratin-19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) were analyzed using the electrochemiluminescence immunoassay and chemiluminescence immunoassay. The receiver operating characteristic curve was performed to analyze the diagnostic efficacy of individual biomarkers in identifying both lung cancer and its histologic subtypes. All six biomarkers showed significantly elevated levels in the lung cancer group compared to both benign pulmonary disease and control groups (P < 0.05). Among the biomarkers evaluated, HE4 exhibited the highest diagnostic performance for lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma with area under the curve (AUC) values of 0.921, 0.891, and 0.937, respectively. ProGRP was the optimal biomarker for small cell lung cancer with an AUC of 0.973. The combination of all six biomarkers yielded the largest AUCs in the diagnosis of lung cancer subtypes (0.937 for lung adenocarcinoma, 0.998 for lung squamous cell carcinoma, and 0.985 for small cell lung cancer). Furthermore, specific combinations, such as HE4 + CEA, HE4 + SCC, and ProGRP + HE4 + NSE, showed strong diagnostic performance in lung cancer. HE4 and its combined detection held substantial clinical significance in the diagnosis of lung cancer and its histologic subtyping, especially for lung adenocarcinoma and lung squamous cell carcinoma.

Contrast-enhanced ultrasound combined with elastic imaging for predicting the efficacy of concurrent chemoradiotherapy in cervical cancer: a feasibility study.

Contrast-enhanced ultrasound (CEUS) and elastography are of great value in the diagnosis of cervical cancer (CC). However, there is limited research on the role of contrast-enhanced ultrasound combined with elastography in predicting concurrent chemoradiotherapy and disease progression for cervical cancer. The purpose of this study was to evaluate the feasibility of contrast-enhanced ultrasound combined with elastography and tumor prognosis. MRI was performed on 98 patients with cervical cancer before and after treatment. Before, during, and 1 week after the treatment, contrast-enhanced ultrasound and elastography were conducted, and the alterations of ultrasound-related parameters at each time point of the treatment were compared. The correlation between contrast-enhanced ultrasound combined with elastic imaging and oncological outcome was assessed. There was no notable difference in overall clinical data between the complete remission (CR) group and the partial remission (PR) group (P>0.05). Before treatment, there were no statistically significant differences in elasticity score, time to peak (TTP), and peak intensity (PI) between the CR group and the PR group. However, there were no statistical differences in elastic strain ratio (SR) and area under the curve (AUC) before and after treatment between the CR group and the PR group, and there were also no statistical differences in the elastic strain ratio (SR) and area under the curve (AUC) of contrast-enhanced ultrasound parameters between the CR group and the PR group before and during treatment. There was a statistically significant difference after treatment (P<0.05).At present, the follow-up of patients is about 1 year, 7 patients were excluded due to loss to follow-up, and 91 patients were included in the follow-up study. Through the review of the cases and combined with MRI (version RECIST1.1) and serology and other related examinations, if the patient has a new lesion or the lesion is larger than before, the tumor marker Squamous cell carcinoma antigen (SCC-Ag) is significantly increased twice in a row, and the patient is divided into progressive disease (PD). Those who did not see significant changes were divided into stable disease (SD) group. The relationship between clinical characteristics, ultrasound parameters and disease progression in 91 patients was compared. There was no significant difference in age and clinical stage between the two groups (P>0.05), but there was a significant difference in the elevation of tumor marker squamous cell carcinoma antigen (SCC-Ag) between the two groups (P<0.05).With the growth of tumors, TTP decreased, elasticity score and PI increased, and the difference was statistically significant (P<0.05). The AUC of SCC-Ag was 0.655, the sensitivity was 85.3%, and the specificity was 45.6%.The AUC, sensitivity and specificity of ultrasound parameters combined with SCC-Ag predicted disease progression was 0.959, 91.2% and 94.8%. Using contrast-enhanced ultrasound and elastography to predict the efficacy and disease progression of concurrent chemoradiotherapy is feasible. In addition, the combination of SCC-Ag with contrast-enhanced ultrasound and elastography can further enhance the efficiency of predicting disease progression.

Integrated pretreatment diffusion kurtosis imaging and serum squamous cell carcinoma antigen levels: a biomarker strategy for early assessment of radiotherapy outcomes in cervical cancer.

This study aims to explore the utility of pretreatment DKI parameters and serum SCC-Ag in evaluating the early therapeutic response of cervical cancer to radiotherapy. A total of 33 patients diagnosed with cervical cancer, including 31 cases of cervical squamous cell carcinoma and two cases of adenosquamous carcinoma, participated in the study. All patients underwent conventional MRI and DKI scans on a 3T magnetic resonance scanner before radiotherapy and after ten sessions of radiotherapy. The therapeutic response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were categorized into a response group (RG), comprising Complete Remission (CR) and Partial Remission (PR), and a non-response group (NRG), comprising Stable Disease (SD) and Progressive Disease (PD). LASSO was employed to select pretreatment DKI parameters, and ROC curves were generated for the selected parameters and serum SCC-Ag. Significant differences were observed in pretreatment MD, Da, Dr, MK, Ka, Kr, and SCC-Ag between the RG and NRG groups (P < 0.01). However, no significant differences were noted for FA and FAK (P = 0.441&0.928). The two selected parameters (MD and MK) demonstrated area under the curve (AUC), sensitivity, and specificity of 0.810, 0.769, 0.850 and 0.827, 0.846, 0.750, respectively. The combination of MD and MK exhibited an improved AUC of 0.901, sensitivity of 0.692, and specificity of 1.000, with a higher Youden index compared to the individual parameters. Conversely, the AUC, sensitivity, and specificity of the combination of MD, MK, and SCC-Ag were 0.852, 0.615, and 1.000, with a Youden index of 0.615. Pretreatment MD, MK, and SCC-Ag demonstrate potential clinical utility, with the combined application of MD and MK showing enhanced efficacy in assessing the early therapeutic response of cervical cancer to radiotherapy. The addition of SCC-Ag did not contribute further to the assessment efficacy.

Sandwich-Like Electrochemical Immunosensing of Squamous Cell Carcinoma Antigen Based on Gold Nanoparticles/Reduced Graphene and Toluidine Blue/UIO-66-NH2

Squamous cell carcinoma antigen (SCCA) is an important biomarker in the diagnose of cancer, so developing effective methods for its detection is of great significance. In the present work, a novel sandwich-like electrochemical immunosensing assay (STEM) of SCCA was constructed by preparing gold nanoparticle/reduced graphene-oxide (Au NPs/rGO) to immobilize primary antibody (PAb) of SCCA and UIO-66-NH2 MOFs structure to immobilize second antibody (SAb) and electroactive toluidine blue (Tb) probe. In this designed STEM assay, the prepared Au NPs/rGO nanohybrid offers the advantages in large surface area and conductivity as carrier, and UIO-66-NH2 provided an ideal platform to accommodate SAb and a large number of Tb molecules as signal amplifier. In the existence of SCCA, the current peaks of Tb from the formed STEM structure increase with the increase of SCCA level. After optimizing the related control factors, a wide linear range (0.01 pg ml−1 and 15.0 ng ml−1) and very low detection limit (0.003 pg ml−1) of SCCA was achieved, it’s thus expected the designed STEM strategy has important applications for the detection of SCCA.

Abstract 5408: SERPINB3 impact on cervical cancer cell mobility and migration

Abstract Cervical cancer is the fourth most common cancer in women, with 311,000 deaths worldwide in 2018. About two thirds of patients with cervical cancer exhibit elevated serum levels of squamous cell carcinoma antigen (SCCA), also known as SERPINB3. SERPINB3 is associated with advanced stage and lymph node metastasis and we have previously shown it has a protective role against radiation treatment and chemotherapy induced cell death. We have also shown that SERPINB3 promotes tumor growth in both immunocompromised and immune competent murine models, yet the molecular mechanism is unknown. We have recently shown that SERPINB3 expression results in activation of signal transducer of transcription 3 (STAT3) and extracellular signal regulated kinase (ERK) in cervical cancer cells. These signaling cascades promote cell proliferation, survival, invasion, and metastasis. Proximity labeling using biotin-ligase fused to SERPINB3 revealed STAT3 and ERK as potential interacting partners. We aim to identify the molecular mechanism by which SERPINB3 promotes tumor progression, and determine if SERPINB3 drives invasion and metastasis in-vivo. We hypothesized that SERPINB3 directly interacts with and activates STAT3 and ERK leading to downstream signaling promoting invasion and metastasis. To test this hypothesis, we used cervical tumor cell lines engineered with SERPINB3 or empty vector control and determined migration by wound healing assay and downstream activation of STAT3 and ERK. Co-immunoprecipitation (co-IP) with western blot was performed to determine an interaction between SERPINB3 and STAT3 and ERK. E6/E7-expressing TC-1, and Lewis Lung Carcinoma cells, LL2, to develop a method for injecting the cervix of immunocompetent c57BL/6 albino mice (no available murine cervical carcinoma line). Wound healing assays revealed that knocking out SERPINB3 shows a decrease in wound closure in both SW756 and HT3 cervical cancer cells compared to control cells, respectively. Co-IP of STAT3 in HT3 cells revealed the presence of SERPINB3, providing further evidence for an interaction between STAT3 and SERPINB3. We were able to grow tumors in the cervix of the C57/BL6 mice and identified potential metastatic deposits in the lung. Moving forward, we plan to identify the minimal functional domain of the interaction between SERPINB3 and STAT3/ERK using a step-wise genetic approach for protein domain deletion. To determine the role of SERPINB3 on metastasis in vivo, we will use, LL2 and TC-1 engineered with the mouse orthologue mSERPINB3a to determine effect of SERPINB3 on invasion and metastasis. Conducting this study will provide insights as to how SERPINB3 may function in a pro-tumor role in cervical cancer and allow the development of SERPINB3-targeted drugs. Citation Format: Marlene L. Campos Guerrero, Li-Yun Chen, Stephanie Markovina. SERPINB3 impact on cervical cancer cell mobility and migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5408.