Squamous Cell Carcinoma Antigen Levels Research Articles

Elevated pretreatment squamous cell Carcinoma Antigen indicates unfavorable treatment outcomes in cervical cancer patients receiving definitive radiotherapy

AbstractObjectiveTo investigate the prognostic value of pretreatment squamous cell carcinoma antigen (SCC Ag) levels for treatment failure prediction in patients with cervical cancer.MethodsA quantity of 985 patients satisfying the eligibility criteria were included, with a median follow‐up duration of 63.7 months. The optimal cutoff value for pretreatment SCC Ag levels was verified by the receiver operating characteristic (ROC) curve. Five‐year disease‐free survival (DFS), overall survival (OS), and local control (LC) rates were evaluated utilizing the Kaplan‐Meier method. Log‐rank test and Cox proportional hazards model was implemented to recognize independent prognostic predictors.ResultsThe optimal pretreatment SCC Ag cutoff value was 8.85 ng/mL. Patients with pretreatment SCC Ag levels ≥ 8.85 ng/mL presented significantly inferior 5‐year DFS (63.8% vs. 81.8%), OS (71.7% vs. 88.7%), and LC (80.5% vs. 91.0%) compared to those with levels < 8.85 ng/mL (all p < 0.001). The results of the multivariate analysis indicated that the pretreatment SCC Ag level was an independent predictor of treatment failure (HR,1.772; 95% CI, 1.366 to 2.299; p < 0.001).ConclusionPretreatment SCC Ag is an effective prognostic factor in patients with cervical cancer undergoing definitive radiotherapy, with a ROC‐identified cutoff value of 8.85 ng/mL and elevated SCC Ag indicates unfavorable outcomes.

Predictive value of serum SCCA and CYFRA21-1 levels on radiotherapy efficacy and prognosis in patients with non-small cell lung cancer

ABSTRACT Monitoring changes in serum tumor marker concentrations can help in the early diagnosis of non-small cell lung cancer (NSCLC). However, there are few methods to monitor the efficacy and prognosis of radiotherapy in NSCLC patients. The present research aimed to explore the correlation between radiotherapy efficacy and squamous cell carcinoma antigen (SCCA) and cytokeratin 19 soluble fragment (CYFRA21-1) levels in NSCLC patients. Serum CYFRA21-1 and SCCA were detected with an automatic chemiluminescence immunoassay analyzer. Patients with NSCLC were followed up by telephone at regular intervals for 35 months. The χ2 test was used to compare clinical characteristics such as age, gender, smoking history and other count data between groups. Predictive value of serum SCCA and CYFRA21-1 on the efficacy of radiotherapy was analyzed by Receiver Operating Characteristic (ROC) curves. The survival of the patients was analyzed by Kaplan–Meier method. The serum SCCA and CYFRA21-1 levels in the NSCLC group were apparently higher by comparison with control group. The SCCA and CYFRA21-1 concentration were both positive relevant to Tumor Node Metastasis (TNM) stage. The Area Under Curve (AUC) of serum SCCA and CYFRA21-1 were 0.732 and 0.721, respectively. In addition, high serum SCCA and CYFRA21-1 levels could predict poor radiotherapy outcomes. Patients with high serum concentration of SCCA and CYFRA21-1 have shorter survival times. High serum SCCA and CYFRA21-1 levels could predict poor prognosis and unfavorable efficacy of radiotherapy in invalids with NSCLC.

Dynamics of level of the tumor-associated marker SCCA in neoadjuvant superselective intra-arterial chemotherapy in patients with cervical squamous cell carcinoma

Background. Evaluation of a tumor-associated marker SCCA (squamous cell carcinoma antigen) level is used in cervical squamous cell carcinoma (CC) to predict the course of the tumor process, monitor the effectiveness of chemo- and chemoradiotherapy, and for preclinical detection of recurrence in follow-up of patients after the completion of primary treatment. However, publications devoted to the study of the possibility of using SCCA level as an additional criterion for the effectiveness of neoadjuvant intra-arterial chemotherapy (IACT) are still rare.Aim. Study of the tumor marker SCCA level in patients with locally advanced squamous CC during neoadjuvant IACT as an additional factor in assessing its effectiveness.Materials and methods. 53 patients with locally advanced squamous CC IB—IVB stages (T1b-3bN0-1M0-1) were included to the study. The mean age of patients was 45.6 years (25-64 years). All patients underwent superselective neoadjuvant IACT with cisplatine (in combination with intravenous administration of docetaxel or paclitaxel). Serum SCCA levels in CC patients were assessed before the first and after the second course of neoadjuvant IACT compared to the clinical effect of treatment after two courses (RECIST 1.1 criteria).Results. SCCA level after 2 courses decreased in all patients with initially increased its level, while the proportion of SCCA-positive cases decreased from 71.7 to 26.4 %. When baseline SCCA values were normal, a complete response was achieved more often than with initially elevated levels (26.7 % vs 15.8 %), while distribution by tumor stages was similar in both subgroups. It has been established that if, after 2 courses of neoadjuvant IACT, SCCA levels exceeds 2.1 ng/ml and/or (for patients with initially increased SCCA value) it decreased by less than 60 % from the baseline, probability to achieve complete response after realization of effect of 2 courses of IACT was extremely small. Strong correlation (R = 0.829) between initial level of SCCA and degree of its decrease after 2 courses of IACT was discovered in the group of patients with complete response after the second course of IACT. It was getting lower in partial response group (R = 0.778) and stabilization group (R = 0.750).Conclusion. Dynamics of SCCA level after 2 courses of IACT in squamous CC patients can be used as additional criterion of the degree of treatment effectiveness.

Clinicopathological and prognosis significance of RIPK1 in patients with cervical squamous cell carcinoma: a retrospective cohort study.

Cervical cancer is one of the most common types of carcinoma in women and has high morbidity and mortality rates worldwide. Recurrent and metastatic disease remains difficult to treat. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors and pattern recognition receptors. This study sought to explore the clinicopathological and prognosis significance of RIPK1 expression in cervical squamous cell carcinoma (CSCC). The data of 100 CSCC patients who underwent curative surgery from 2019 to 2020 were retrospectively included in this study. We collected the clinicopathological information of the patients and detected RIPK1 protein expression using immunohistochemistry. The Chi-square test and a 1-way analysis of variance were used to make comparisons between groups stratified by RIPK1 expression. A Pearson linear correlation analysis was used to evaluate the association between RIPK1 expression and the clinicopathological characteristics of the patients. A Cox regression analysis and Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS). A multivariable regression analysis was conducted to identify the risk factors for an impaired prognosis in CSCC. RIPK1 was found to be overexpressed in the CSCC tissues. RIPK1 expression was significantly associated with age, the preoperative serum squamous cell carcinoma antigen (SCC-Ag) level, lymph node metastasis, invasion depth, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, PFS, and OS (P<0.05). The PFS and OS differed significantly among patients with RIPK1 expression (P<0.05). The multivariate analysis showed that RIPK1 was not independent risk factors for PFS and OS in CSCC patients (P>0.05). The expression of RIPK1 was significantly upregulated in CSCC and was associated with the clinicopathological features of CSCC. RIPK1 might serve as a novel marker that can be used to predict the prognosis of CSCC patients and as a biological target for the treatment of CSCC.

Correlation between HRCT signs and levels of CA125, SCCA, and NSE for different pathological types of lung cancer.

The aim of this study was to investigate the correlation between high-resolution CT (HRCT) signs and serum tumor markers, to improve the diagnostic level and identify different pathological types of lung cancer. 102 patients with pathologically confirmed lung cancer were selected as the observation group. HRCT scan and serum tumor markers [cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCCA), and neuron-specific enolase (NSE)] were performed to analyze the correlation. Among the 102 cases of lung cancer, 88 cases were of lobulation sign, 78 cases of speculation sign, 45 cases of pleural indentation sign, 35 cases of vessel tracking sign, and 34 cases of vacuole sign. CA125 had the highest concentration in lung adenocarcinoma (55.74±14.18) ng/ml, and SCCA had the highest concentration in lung squamous cell carcinoma (18.98±6.37) ng/ml. The concentration of NSE in small cell lung cancer was the highest (48.12±16.19) ng/ml. Pleural indentation sign and vacuole sign were more likely to happen in lung adenocarcinoma and lung squamous cell carcinoma, respectively. The significant increase of CA125, SCCA, and NSE concentrations suggested that lung cancer patients were more likely to suffer from lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer, respectively.

High Sensitive and Specific Detection of SCCA via Halloysite Nanotube Modified Terahertz Metasurface Sensor

Squamous cell carcinoma antigen (SCCA) level is an auxiliary indicator for lung cancer diagnosis and predictive monitoring, and its standard reference value is less than 1.5 ng/mL. Therefore, achieving high sensitivity and specific detection of the SCCA is a challenge. In this work, we designed a double split-ring-resonator (SRR) terahertz (THz) metasurface sensor. Simulation results show that the sensitivity of the sensor can reach 103 GHz/RIU (refractive index unit). After the sensor is modified with different concentrations of halloysite nanotubes (HNTs), the resonant frequency of the sensor exhibits different linear responses to different concentrations of SCCA. The optimum concentration of HNTs to enhance the detection performance of the sensor was obtained as 10 mg/mL. The linear range of SCCA concentration of the HNT modified sensor was 1 pg/mL to 100 ng/mL. On this basis, we modified anti-SCCA on the sensor, and other biomarkers of carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), CA125, and CA199 were used as comparisons. The results indicated that the sensor modified with HNTs showed a more remarkable frequency shift for the SCCA, which verified that the sensor had good specificity for the SCCA. Therefore, this sensor can be used for highly sensitive and specific detection of the SCCA.

Significantly higher serum levels and positive rates of tumor biomarkers in patients with oral lichen planus

Background/purposeOral lichen planus (OLP) is generally considered as an oral potentially malignant disorder (OPMD). Previous studies have shown significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma-antigen (SCC-Ag), and ferritin levels in patients with OPMDs such as oral submucous fibrosis, oral leukoplakia, oral erythroleukoplakia, or oral verrucous hyperplasia. This study aimed to evaluate whether there were significantly higher serum levels and positive rates of CEA, SCC-Ag, and ferritin in OLP patients than in healthy control subjects. Materials and methodsThe serum CEA, SCC-Ag, and ferritin levels in 106 OLP patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. ResultsThis study found significantly higher mean serum CEA and ferritin levels in 106 OLP patients than in 187 healthy control subjects. Moreover, 106 OLP patients had significantly higher serum positive rates of CEA (12.3%) and ferritin (33.0%) than 187 healthy control subjects. Although the mean serum SCC-Ag level was higher in 106 OLP patients than in 187 healthy control subjects, the difference was not statistically significant. Of the 106 OLP patients, 39 (36.8%), 5 (4.7%), and 0 (0.0%) had serum positivities of one, two, or three tumor biomarkers including CEA, SCC-Ag, and ferritin, respectively. ConclusionOur findings indicate significantly higher serum levels and positive rates of CEA and ferritin in OLP patients than in healthy control subjects.

Establishment of a risk stratification model based on the combination of post-treatment serum squamous cell carcinoma antigen levels and FIGO stage of cervical cancer for treatment and surveillance decision-making

ObjectiveTo develop a risk stratification model based on the International Federation of Gynecology and Obstetrics (FIGO) staging combined with squamous cell carcinoma antigen (SCC-Ag) for the classification of patients with cervical squamous cell carcinoma (CSCC) into different risk groups.MethodsWe retrospectively reviewed the data of 664 women with stage IIA–IVB CSCC according to the 2018 FIGO staging system who received definitive radiotherapy from March 2013 to December 2017 at the department of radiation oncology of Sun Yat-sen University Cancer Center. Cutoff values for continuous variables were estimated using receiver operating characteristic curve analysis. Using recursive partitioning analysis (RPA) modeling, overall survival was predicted based on the prognostic factors determined via Cox regression analysis. The predictive performance of the RPA model was assessed using the consistency index (C-index). Intergroup survival differences were determined and compared using Kaplan–Meier analysis and the log-rank test.ResultsMultivariate Cox regression analysis identified post-treatment SCC-Ag (< 1.35 ng/mL and > 1.35 ng/mL; hazard ratio (HR), 4.000; 95% confidence interval (CI), 2.911–5.496; P < 0.0001) and FIGO stage (II, III, and IV; HR, 2.582, 95% CI, 1.947–3.426; P < 0.0001) as the independent outcome predictors for overall survival. The RPA model based on the above prognostic factors divided the patients into high-, intermediate-, and low-risk groups. Significant differences in overall survival were observed among the three groups (5-year overall survival: low vs. intermediate vs. high, 91.3% vs. 76.7% vs. 29.5%, P < 0.0001). The predictive performance of the RPA model (C-index, 0.732; 95% CI, 0.701–0.763) was prominently superior to that of post-treatment SCC-Ag (C-index, 0.668; 95% CI, 0.635–0.702; P < 0.0001) and FIGO stage (C-index, 0.663; 95% CI, 0.631–0.695; P < 0.0001).ConclusionsThe RPA model based on FIGO staging and post-treatment SCC-Ag can predict the overall survival of patients with CSCC, thereby providing a guide for the formulation of risk-adaptive treatment and individualized follow-up strategies.

Immunohistological study of ovarian mature cystic teratoma with extremely elevated SCC antigen level

Squamous cell carcinoma (SCC) antigen is a reliable tumor marker for various cancers, including cervical cancer and lung cancer, and was recently reported to correlate with the severity of inflammatory skin diseases such as atopic dermatitis. Herein, we present a case of a 47-year-old female patient who presented with acute abdomen rupture due to a mature cystic teratoma of the ovary, approximately 11 cm in diameter on imaging examination, prompting emergency laparoscopic surgery. The patient had no symptoms of atopic dermatitis. The operative findings showed no evidence of torsion, but the membrane was partially ruptured, leading to the leakage of the cyst contents. The operation was completed after excising the adnexa and intraperitoneal lavage. The postoperative results revealed a markedly high serum SCC antigen level of 55.3 ng/dL, which was normalized at 2 months postoperatively. Postoperative histopathological examination revealed no squamous cell carcinoma component but a marked lymphocytic infiltrate under the squamous epithelium, suggesting a high degree of inflammation. Additionally, immunostaining demonstrated a cluster of differentiation (CD) 8+ lymphocyte predominance over CD4+ lymphocytes, similar to the histology of atopic dermatitis. Altogether, our findings suggest that the abnormally high SCC antigen levels might be attributed to the presence of severe inflammation in the mature cystic teratoma rather than an underlying malignancy and support the notion that SCC antigen may be a useful marker beyond its established role in cervical and lung cancers.

Clinical utility of pretreatment serum squamous cell carcinoma antigen for prognostication and decision-making in patients with early-stage cervical cancer.

To investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC). We enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes. Recursive partitioning analysis (RPA) was used to construct a risk stratification model for overall survival (OS). The performance of the RPA-based model was assessed using a receiver operating characteristic (ROC) curve. RCS analysis revealed an association between SCCA and OS and disease-free survival (DFS); SCCA ⩾2.5 ng/mL was robust for risk discrimination in our cohort. SCCA had an interaction effect with FIGO classification: Patients with FIGO I and SCCA ⩾2.5 ng/mL overlapped with those with FIGO II and SCCA < 2.5 ng/mL for OS [hazard ratio, 1.04 (95% confidence interval (CI): 0.49-2.24), p = 0.903] and DFS [1.05 (0.56-1.98), p = 0.876]. RPA modeling incorporating SCCA (<2.5 ng/mL and ⩾2.5 ng/mL) and FIGO classification divided CC into three prognostic groups: RPA I, FIGO stage I, and SCCA < 2.5 ng/mL; RPA II, FIGO stage I, and SCCA ⩾ 2.5 ng/mL, or FIGO stage II and SCCA < 2.5 ng/mL; and RPA III, FIGO stage II, and SCCA ⩾ 2.5 ng/mL; with 5-year OS of 94.0%, 85.1%, and 73.5%, respectively (p < 0.001). ROC analysis confirmed that the RPA model outperformed the FIGO 2018 stage with significantly improved accuracy for survival prediction [area under the curve: RPA versus FIGO, 0.663 (95% CI: 0.619-0.705] versus 0.621 (0.576-0.664), p = 0.045]. Importantly, the RPA groupings were associated with the efficacy of treatment regimens. Surgery followed by adjuvant treatment had a higher OS (p < 0.01) and DFS (p = 0.024) than other treatments for RPA III, whereas outcomes were comparable among treatment regimens for RPA I-II. Herein, the role of SCCA for prognostication was confirmed, and a robust clinicomolecular risk stratification system that outperforms conventional FIGO classification in early-stage squamous and adenosquamous CC was presented. The model correlated with the efficacy of different treatment regimes.

RESOLVE-DWI-based deep learning nomogram for prediction of normal-sized lymph node metastasis in cervical cancer: a preliminary study

BackgroundIt is difficult to predict normal-sized lymph node metastasis (LNM) in cervical cancer clinically. We aimed to investigate the feasibility of using deep learning (DL) nomogram based on readout segmentation of long variable echo-trains diffusion weighted imaging (RESOLVE-DWI) and related patient information to preoperatively predict normal-sized LNM in patients with cervical cancer.MethodsA dataset of MR images [RESOLVE-DWI and apparent diffusion coefficient (ADC)] and patient information (age, tumor size, International Federation of Gynecology and Obstetrics stage, ADC value and squamous cell carcinoma antigen level) of 169 patients with cervical cancer between November 2013 and January 2022 were retrospectively collected. The LNM status was determined by final histopathology. The collected studies were randomly divided into a development cohort (n = 126) and a test cohort (n = 43). A single-channel convolutional neural network (CNN) and a multi-channel CNN based on ResNeSt architectures were proposed for predicting normal-sized LNM from single or multi modalities of MR images, respectively. A DL nomogram was constructed by incorporating the clinical information and the multi-channel CNN. These models’ performance was analyzed by the receiver operating characteristic analysis in the test cohort.ResultsCompared to the single-channel CNN model using RESOLVE-DWI and ADC respectively, the multi-channel CNN model that integrating both two MR modalities showed improved performance in development cohort [AUC 0.848; 95% confidence interval (CI) 0.774–0.906] and test cohort (AUC 0.767; 95% CI 0.613–0.882). The DL nomogram showed the best performance in development cohort (AUC 0.890; 95% CI 0.821–0.938) and test cohort (AUC 0.844; 95% CI 0.701–0.936).ConclusionThe DL nomogram incorporating RESOLVE-DWI and clinical information has the potential to preoperatively predict normal-sized LNM of cervical cancer.

Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China

ObjectivesTo describe the prevalent distribution of human papilloma virus (HPV) infection in patients with early-stage cervical squamous cell carcinoma (CSCC). To provide data on high-risk HPV (HR-HPV) infection and other clinicopathological factors for their correlations with the survival of CSCC patients.MethodsA total of 1425 patients with FIGO stages IA to IIA CSCC who underwent radical surgery between September 2008 and December 2012 were enrolled in the study. The prevalent distribution of HPV infection with different patient characteristics and survivals were analyzed with or without propensity score matching (PSM).ResultsThe overall infection rate of HPV was 84.3%, including 13 carcinogenic HR-HPV genotypes and 8 low-risk HPV genotypes with infection rates of 82.6% and 5.8%, respectively. The distribution of HPV infection were proportional in patients with either different age groups or different FIGO stages. HPV16 was the dominant subtype with an infection rate of 65.1%, followed by the other top four subtypesHPV58 (8.7%), 18 (7.7%) and 52 (4.5%). χ2 analysis revealed that increased preoperative serum squamous cell carcinoma antigen levels and lymphovascular space invasion (LVSI) were statistically associated with HPV status. However, regression analyses indicated that only deep stromal invasion, LVSI and lymph node metastasis were independent prognostic factors on 5-year overall survival (OS), but not HR-HPV infection status even in the second exploratory analysis (P = 0.939) based on the PSM applied to reduce selection bias.ConclusionsThis study provided baseline data on the prevalence characteristics of HPV infections in patients with early-stage CSCC, and HR-HPV infection was not a prognosticator of 5-year OS, other than FIGO stage, LVSI and lymph node metastasis.

Changes of T Lymphocyte Subsets in Peripheral Blood of Patients with Intermediate and Advanced Cervical Cancer before and after Nimotuzumab Combined with Chemoradiotherapy

Introduction: Cervical cancer (CC) is the main malignant tumor of gynecology with high mortality. This study aimed to explore the changes of T lymphocyte subsets in the peripheral blood of patients with intermediate and advanced CC (IACC) treated with nimotuzumab (Nimo) combined with chemoradiotherapy (CRT). Methods: Peripheral blood was extracted before and after treatment, and patients were randomly divided into the CRT group (N = 68) or the Nimo + CRT group (N = 68). The levels of tumor markers squamous cell carcinoma antigen (SCCA), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA), tumor indexes leptin and insulin-like growth factor-2 (IGF2), and key secretory factors (interferon γ/tumor necrosis factor α/interleukin (IL)-4/IL-13) of Th1 and Th2 cells in the serum were detected. The levels of T lymphocyte subsets CD3+, CD4+, CD8+, and CD4+/CD8+ and the levels of Th1/Th2 and Th17/Treg in CD4+ cell subsets were determined by flow cytometry. The objective remission rate, progression-free survival (PFS), and overall survival (OS) of patients were analyzed, and Kaplan-Meier curves were drawn to show the prognosis of patients. Results: After treatment, the levels of SCCA, CA125, CEA, leptin, and IGF2 in the serum of patients with IACC were decreased, the level of Th1/Th2 was increased, and the Th17/Treg level was decreased. The treatment effect of Nimo + CRT was more significant than that of CRT alone. Survival curve analysis showed that Nimo + CRT could prolong PFS and OS in patients with IACC. In addition, the follow-up results of patients showed that Nimo did not increase the incidence and severity of adverse reactions caused by CRT. Conclusion: Nimo combined with CRT can protect the immune function of patients, improve the effective rate, and prolong the survival rate of patients with IACC.

Clinical Efficacy of Antianlotinib Combined with Immune Checkpoint Inhibitors in the Treatment of Advanced Non-Small-Cell Lung Cancer and Its Effect on Serum VEGF, CEA, and SCC-Ag.

Purpose This study is aimed at investigating the clinical safety and effectiveness of anlotinib combined with immune checkpoint inhibitors (ICIs) in the treatment of non-small-cell lung cancer (NSCLC). Methods We selected 68 NSCLC patients treated at the Tumor Hospital Affiliated to Nantong University from October 2019 to January 2022. Patients receiving ICI monotherapy were included in the control group (n = 36), whereas patients receiving anlotinib combined with ICIs were enrolled in the study group (n = 32). The survival, adverse reactions (AEs), and short-term clinical effectiveness of the two groups were observed. The tumor markers (vascular endothelial growth factor (VEGF), carcino-embryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-AG)) and T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+) were determined before and after treatment. Results Compared with the control group, the disease-control rate (DCR) and objective response rate (ORR) in the study group were substantially higher than that of the control group (62.50 vs. 36.11, 81.25 vs. 55.56; P < 0.05). The serum levels of VEGF, CEA, and SCC-AG in the two groups were considerably lower after two cycles of treatment (P < 0.05), and the serum levels of VEGF, CEA, and SCC-AG in the study group were significantly lower than those in the control group (P < 0.05). Following therapy, CD8+ in both groups decreased dramatically (P < 0.05), whereas CD3+, CD4+, and CD4+/CD8+ were significantly increased, but there was no statistical difference between the two groups (P > 0.05). The incidence of gastrointestinal, respiratory, cardiovascular, and immune-related adverse events did not significantly differ between the two groups (P > 0.05). The median progression-free survival (PFS) in the control and study groups for the first-line treatment patients was 7.2 and 9.8 months, respectively, whereas for the second-line treatment patients, it was 4.2 and 6.4 months, respectively. The mean PFS of study group was substantially longer than that of the control group regardless of the first- or second-line treatment. According to Cox analysis, the number of drug lines and TNM stage was independent risk variables impacting the prognosis of patients in this study. Conclusion The combination of anlotinib with ICIs was more effective than either agent alone in the first- and second-line treatment of patients with advanced NSCLC. This treatment regimen did not interfere with immunological recovery or increase side effects.

High Serum Squamous Cell Carcinoma Antigen Level Associated with Remission of Mild/Moderate Dysplasia of the Esophagus: A Nested Case-Control Study.

Background The esophageal epithelial dysplasia is the precancerous lesion. This study aimed to investigate the association between the serum squamous cell carcinoma antigen (SCCA) and the remission of esophageal squamous mild or moderate dysplasia. Methods We performed a nested case–control study. Patients with mild/moderate dysplasia of the esophageal squamous epithelium were enrolled in this study during the years of 2013–2015 and received a follow-up endoscopy during 2017–2018. With the comparison between baseline and follow-up diagnosis, the patients were divided into regression/stable and progression groups. A predictive model for the outcome of dysplasia was comprised of the variables of SCCA, age, sex, education level, and baseline dysplasia grade. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficacy of the regression status of dysplasia under the predictive model. Results There were 146 patients enrolled in this study. 100 patients experienced a regression or stable status of dysplasia and 46 patients had a progressed status. Increased age, low education level, and moderate dysplasia were the risk factors of progression. With an 0.1 μg/L increase, SCCA was associated with a 0.90-fold risk (95% CI 0.81, 0.99) of progression. In the predictive model, the area under ROC curve was 0.78. The cut-off values of predictive probability of combined factors for progression, were 0.40 and 0.32 for males and females, respectively. Conclusions Increased serum SCCA concentration was associated with regressed severity of mild and moderate dysplasia of the esophageal mucosa. Further studies were warranted and SCCA concentration was a potential biomarker for the dysplasia prognosis.

CXCL10 serves as a potential serum biomarker complementing SCC-Ag for diagnosing cervical squamous cell carcinoma

BackgroundCervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease.MethodsWe investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated.ResultsThe two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels.ConclusionsThe results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.

A microfluidic chip using Au@SiO2 array–based highly SERS-active substrates for ultrasensitive detection of dual cervical cancer–related biomarkers

In this work, a microfluidic chip using Au@SiO2 array-based highly active SERS substrates was developed for quantitative detection of squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) associated with cervical cancer. The chip consisted of six functional units with pump-free design, enabling parallel detection of multiple samples in an automatic manner without external pumps and improving the portability. Ag nanocubes (AgNCs) were labeled with Raman reporters and coupled with antibodies (labeling) to prepare SERS tags, while the Au nanoparticle-modified SiO2 microsphere (Au@SiO2) array was conjugated with antibodies (coating) to generate the highly SERS-active capturing substrate. In the presence of target biomarkers, they were captured by SERS tags and capturing substrate, resulting in the formation of "sandwich" structures which were trapped in the detection chamber. As the immune reaction proceeded, a large number of "hot spots" were generated by the proximity of the Au@SiO2 array substrate and AgNCs, greatly amplifying SERS signals. With this chip, the limits of detection of the SCCA and CEA levels in human serum were estimated to be as low as 0.45pgmL-1 and 0.36pgmL-1, respectively. Furthermore, the good selectivity and reproducibility of this chip were confirmed. Finally, clinical serum samples were analyzed by this chip, and the outcomes were consistent with those of enzyme-linked immunosorbent assay (ELISA). Thus, the proposed microfluidic chip can be potentially applied for the clinical diagnosis of cervical cancer.

Clinical analysis of 13 cases of primary squamous-cell thyroid carcinoma.

ObjectiveTo analyze the clinical features, ultrasonographic manifestations, pathological features, treatment and prognosis of primary thyroid squamous cell carcinoma (PSCTC) and summarize the experience in diagnosis and treatment of this condition.MethodsA retrospective analysis was conducted on patients who were admitted to Zhejiang Cancer Hospital from 2007 to 2021 due to thyroid nodules or thyroid malignant tumors that were ultimately confirmed by postoperative pathology as primary thyroid squamous cell carcinoma. We summarize the general situation, clinical information, laboratory examination, ultrasonic image characteristics, pathological examination, clinical treatment and prognosis of the patients.ResultsPSCTC is most often seen in older men and progresses rapidly. In laboratory tests, some patients had elevated levels of tumor markers (CA199, squamous cell carcinoma antigen level), thyroglobulin levels and tumor-related substances, but all these indicators lacked specificity. The ultrasound features of PSCTC are mainly hypoechoic, hard, substantial nodules with gross borders and a grade 1-2 blood flow signal, sometimes with signs of necrosis and calcification. In terms of treatment, PSCTC is mainly surgically resected, though some patients in this study underwent iodine-131 radiation therapy, local radiotherapy, and chemotherapy with unclear results. None of the patients survived for very long after treatment, but the prognosis of patients with highly differentiated squamous carcinoma was significantly better than that of patients with poorly differentiated squamous carcinoma. Papillary thyroid carcinoma may be one of the causes of PSCTC.ConclusionPSCTC is a malignant tumor with high malignancy and rapid clinical progression. Treatment options are mainly based on surgical resection and can be supplemented with radiotherapy and chemotherapy, but there is still a lack of a standardized treatment management system, and more cases and reports are needed to accumulate data.

Association between squamous cell carcinoma antigen level and EGFR mutation status in Chinese lung adenocarcinoma patients.

BackgroundTo investigate the association between squamous cell carcinoma antigen (SCCAg) level and epidermal growth factor receptor (EGFR) mutation status in Chinese lung adenocarcinoma patients.MethodsWe retrospectively analyzed 293 patients with lung adenocarcinoma, divided into EGFR mutant group (n = 178) and EGFR wild‐type group (n = 115). The general data and laboratory parameters of the two groups were compared. We used univariable and multivariable logistic regression to analyze the association between SCCAg level and EGFR mutation. Generalized additive model was used for curve fitting, and a hierarchical binary logistic regression model was used for interaction analysis.ResultsSquamous cell carcinoma antigen level in the EGFR wild‐type group was significantly higher than that in the mutant group (p < 0.001). After adjusting for confounding factors, we found that elevated SCCAg was associated with a lower probability of EGFR mutation, with an OR of 0.717 (95% CI: 0.543–0.947, p = 0.019). For the tripartite SCCAg groups, the increasing trend of SCCAg was significantly associated with the decreasing probability of EGFR mutation (p for trend = 0.015), especially for Tertile 3 versus Tertile 1 (OR = 0.505; 95% CI: 0.258–0.986; p = 0.045). Curve fitting showed that there was an approximate linear negative relationship between continuous SCCAg and EGFR mutation probability (p = 0.020), which was first flattened and then decreased (p < 0.001). The association between the two was consistent among different subgroups, suggesting no interaction (all p > 0.05).ConclusionThere is a negative association between SCCAg level and EGFR mutation probability in Chinese lung adenocarcinoma patients.

Single Nucleotide Polymorphisms of EXOC1, BCL2, CCAT2, and CARD8 Genes and Susceptibility to Cervical Cancer in the Northern Chinese Han Population.

Cervical cancer (CC) is one of the main malignant tumors that threaten the health and lives of women around the world, and its morbidity and mortality rate ranks fourth. At present, most studies on the genetic background of CC focus on genetic polymorphisms. Single nucleotide polymorphisms (SNPs) are considered clinically as potential diagnostic and therapeutic biomarkers for a variety of tumors. Therefore, we aimed to explore the association between SNPs in different genes (EXOC1 gene, BCL2 gene, CCAT2 gene and CARD8 gene) and susceptibility to CC. This study is a case-control study based on women in northern Chinese, which included 492 women with CC and 510 healthy women. This study used multiplex PCR combined with next-generation sequencing to genotype the selected SNPs (rs13117307(C/T) in EXOC1 gene, rs2279115(C/A) in BCL2 gene, rs6983267(G/T) in CCAT2 gene and rs7248320(G/A) in CARD8 gene). The results of the study showed that there was no significant association between the four SNPs and the susceptibility to CC. However, in further stratified analysis, we found that rs13117307 and rs2279115 were significantly related to squamous cell carcinoma antigen (SCC-Ag) levels in women with CC, and rs6983267 was significantly related to the menopausal status of women with CC. Specifically, alleles T of rs13117307 and genoytpe AA of rs2279115 when SCC-Ag is greater than 1.5 ng/ml increase the risk of CC. The genotype TG/TG+TT of rs6983267 increases the risk of CC in premenopausal women. In conclusion, although we did not directly find a significant correlation between four SNPs, rs13117307 in EXOC1 gene,rs2279115 in BCL2 gene, rs6983267 in CCAT2 gene and rs7248320 in CARD8 gene, and CC susceptibility, we found that SNPs rs13117307, rs2279115, rs6983267 were associated with the clinical characteristics of several patients' CC patients. Therefore, this study provides us with new ideas for understanding CC and the diagnosis and treatment of CC in the future.