Squamous Cell Carcinoma Antigen Research Articles

Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes.

The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.

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 &lt; 8.85 ng/mL (all p &lt; 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 &lt; 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.

Unilateral ovarian recurrence 5 years after hysterectomy for microinvasive squamous cervical cancer stage IA1: a rare case report

BackgroundOvarian metastasis or recurrence of cervical microinvasive squamous cell carcinoma (SCC) is very rare. We report a case of unilateral ovarian recurrence 5 years after hysterectomy for the SCC stage IA1 without lymph vascular space invasion (LVSI).Case presentationA 49-year-old female patient suffered from a dull pain in the left lower abdomen for 3 months. And five years ago, she received a laparoscopic hysterectomy for the treatment of stage IA1 (without LVSI) SCC of the cervix. The level of squamous cell carcinoma antigen (SCC-Ag) in serum was significantly elevated (10.60 ng/mL). Pelvic magnetic resonance imaging (MRI) revealed a left ovarian solid tumor measuring 5.5 × 3.9 × 5.6 cm with heterogeneous enhancement. During laparotomy, the left ovarian tumor was measured about 5.0 × 4.5 × 3.0 cm and seemed densely adherent to the posterior peritoneal wall, including the left ureter. The tumor and pelvic lymph node were carefully removed. Postoperative anatomy revealed a solid mass with a greyish-white section. Postoperative pathology showed recurrent moderately differentiated ovarian SCC with negative pelvic lymph nodes. Immunohistochemistry showed that the tumor cells were positive for P16, P63, P40, and CK5/6 markers, and the positive rate of Ki67 was about 80%.ConclusionsOvary preservation is reasonable and appropriate in young patients with microinvasive SCC. Ovarian recurrence is rare, but gynecological oncologists should not overlook its possibility. The serum SCC-Ag is an important indicator for monitoring postoperative disease progression.

Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects

Squamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Collectively, these findings suggest that bi-allelic SART3 variants underlie a spliceosomopathy which we tentatively propose be termed INDYGON syndrome (Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XYGONadal dysgenesis). Our findings will enable additional diagnoses and improved outcomes for individuals born with this condition.

Comparison of Oncologic Outcomes between Radical Hysterectomy and Primary Concurrent Chemoradiotherapy in Women with Bulky IB and IIA Cervical Cancer under Risk Stratification.

To stratify patients according to tumor marker and histology and compare the survival outcome between radical hysterectomy (RH) and primary concurrent chemoradiotherapy (CCRT) in bulky IB and IIA cervical cancer. A total of 442 patients with cervical cancer were enrolled in the Chang Gung Research Database from January 2002 to December 2017. Patients with squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA) ≥10 ng/mL, adenocarcinoma (AC), or adenosquamous carcinoma (ASC) were stratified into the high-risk (HR) group. The others were classified into the low-risk (LR) group. We compared oncology outcomes between RH and CCRT in each group. In the LR group, 5-year overall survival (OS) and recurrence-free survival (RFS) were 85.9% vs. 85.4% (p = 0.315) and 83.6% vs. 82.5% (p = 0.558) in women treated with RH (n = 99) vs. CCRT (n = 179), respectively. In the HR group, the 5-year OS and RFS were 83.2% vs. 73.3% (p = 0.164) and 75.2% vs. 59.6% (p < 0.036) in patients treated with RH (n = 128) vs. CCRT (n = 36), respectively. Regarding recurrence, locoregional recurrence (LRR) (8.1% vs. 8.6%, p = 0.812) and distant metastases (DM) (17.8% vs. 21%, p = 0.609) were similar between RH and CCRT in the LR group. However, lower LRR (11.6% vs. 26.3%, p = 0.023) but equivalent DM (17.8% vs. 21%, p = 0.609) were found for women undergoing RH compared with CCRT in the HR group. There were similar survival and recurrence rates between both treatment modalities in low-risk patients. Meanwhile, primary surgery with or without adjuvant radiation provides better RFS and local control in women with high-risk features. Further prospective studies are needed to confirm these findings.

Effect of neoadjuvant therapy on serum transforming growth factor-β, squamous cell carcinoma associated antigen, and prognosis in patients with locally advanced esophageal cancer.

It was to explore the effect of neoadjuvant therapy (NAT) on serum-related indicators and prognosis of patients with locally advanced esophageal cancer (EC). 400 EC patients were grouped as controls (295 cases, radical EC resection alone) and research group (105 cases, NAT plus radical EC resection). The levels of serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), programmed death-1 (PD-1), PD-2, transforming growth factor-β1 (TGF-β1), and squamous cell carcinoma (SCC) antigen were detected before and after treatment. The follow-up lasted for 3 years. The quality of life (QoL) was evaluated by QLQ-OES24. The recurrence rate, recurrence time, overall survival rate (SR), disease-free SR, and complication rate were compared. Compared with controls, the levels of serum CA19-9, CEA, CYFRA21-1, PD-1, PD-2, TGF-β1, and SCC were decreased, the QoL score was increased 3 years post-treatment, and the recurrence time was prolonged in the research group (P<0.05). The R0 resection rate, recurrence rate, 3-year overall SR, and disease-free SR of the two groups were 67.12% vs 85.71%, 21.36% vs 6.67%, 56.27% vs 77.14%, 29.83% vs 45.71%, respectively (P<0.05). The complication rates of the two groups were 32.54% and 29.52%, respectively (P>0.05). NAT plus radical resection of EC can effectively reduce the level of serum oncology markers in patients with locally advanced EC, reduce the postoperative recurrence rate, improve QoL and SR, and has high safety.

Prognostic impact of perioperative change in serum p53 antibody titers in esophageal squamous cell carcinoma.

The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC. From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups. There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2months vs. 36.7months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS. Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.

An electrochemiluminescence immunosensor with double co-reaction accelerators based on Ag3PO4@EuPO4-AgNP for detecting squamous cell carcinoma antigen.

This study aimed to design a sandwich electrochemiluminescence (ECL) immunosensor with double co-reaction accelerators for sensitively detecting squamous cell carcinoma antigen (SCCA). First, silver orthophosphate (Ag3PO4) nanoparticles were modified on the surface of EuPO4 nanowires to improve their poor dispersibility/solubility. At the same time, EuPO4 was used as a co-reaction accelerator to catalyze S2O82- to produce more intermediates (SO4•-), significantly enhancing the ECL signal of Ag3PO4. Ag nanoparticles (AgNP) modified on Ag3PO4@EuPO4 composite nanomaterials were used not only as linkers of luminescence groups and biomarkers but also as a co-reaction accelerator to effectively enhance ECL signal. The designed ECL immunosensor displayed several advantages, including good stability and reproducibility. Under the optimal conditions, its linear range in detecting SCCA was 0.0001-50ng·mL-1, the detection limit was 25fg·mL-1 (S/N = 3), the recovery was 96.6-100.4%, and the relative standard deviation was less than 4.8%. It was successfully applied todetect SCCA in human serum.

Intensity-modulated radiotherapy and cisplatin-based chemotherapy for anal cancer: long-term outcomes at a single institution.

To evaluate oncological outcomes and late toxicities in a retrospective series of patients with locally-extended anal squamous cell carcinoma (ASCC), treated with curative Intensity Modulated Radiotherapy (IMRT) and chemotherapy. ASCC patients who underwent chemo-radiotherapy with IMRT from 2010 to 2020 were included. Oncological outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS) and event-free survival (EFS). Late toxicity was detected according to CTCAE v.5.0 and RTOG late radiation morbidity scoring system. Ninety-five patients were included. Most patients (83%) received chemotherapy with oral Fluoropyrimidine plus Cisplatin. The median follow-up was 5.5years. The OS was 85.2%, 82.1% and 79.3% at 3, 5 and 8years, respectively. The DFS was 73.1%, 70%, and 65.3% at 3, 5 and 8years, respectively; 3, 5 and 8years CFS was 86.2%, 84.3% and 84.3%, respectively. The EFS was 71%, 67.9% and 63.1%, at 3, 5 and 8years, respectively. On univariable analysis, a statistically significant lower OS was found for patients with T3-T4 stage (HR = 4.58, p = 0.005) and overall treatment time (OTT) ≥ 47days (HR = 3.37, p = 0.038). A statistically significant lower DFS was reported for patients with T3-T4 stage (HR = 2.72, p = 0.008) and Serum Squamous Cell Carcinoma Antigen (SCC) value post-RT > 1.5 (HR = 2.90, p = 0.038.). Ten severe late toxicity (≥ G3) events were reported in 8 patients (8.6%). Our data confirm IMRT concomitant with a Cisplatin-based chemotherapy as an effective treatment of ASCC, ensuring acceptable long-term toxicities and good oncological 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.

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.

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.

The predictive value of chest computed tomography images, tumor markers, and metabolomics in the identification of benign and malignant pulmonary nodules.

Invasive puncture biopsy is currently the main method of identifying benign and malignant pulmonary nodules (PNs). This study aimed to investigate the application effect of chest computed tomography (CT) images, tumor markers (TMs), and metabolomics in the identification of benign and malignant PNs (MPNs). A total of 110 patients with PNs who were hospitalized in Dongtai Hospital of Traditional Chinese Medicine from March 2021 to March 2022 were selected as the study cohort. A retrospective analysis study of chest CT imaging, serum TMs testing, and plasma fatty acid (FA) metabolomics was performed on all participants. According to the pathological results, participants were divided into a MPN group (n=72) and a benign PN (BPN) group (n=38). The morphological signs of CT images, the levels and positive rate of serum TMs, and the plasma FA indicator were compared between groups. There were significant differences between the MPN group and the BPN group in the CT morphological signs, including location of PN and the number of patients with or without lobulation sign, spicule sign, and vessel convergence sign (P<0.05). Serum carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC-Ag) were not significantly different between the 2 groups. The serum contents of CEA and CYFRA 21-1 in the MPN group were remarkably higher than those in the BPN group (P<0.05). The plasma levels of palmitic acid, total omega-3 polyunsaturated FA (W3), nervonic acid, stearic acid, docosatetraenoic acid, linolenic acid, eicosapentaenoic acid, total saturated FA, and total FA were much higher in the MPN group than the BPN group (P<0.05). In conclusion, chest CT images and TMs, combined with metabolomics, has a good application effect in the diagnosis of BPNs and MPNs, and is worthy of further promotion.

A Nomogram Incorporating Neutrophil-to-Lymphocyte Ratio and Squamous Cell Carcinoma Antigen Predicts the Prognosis of Oral Cancers.

We introduced a novel squamous cell carcinoma inflammatory index (SCI) and explored its prognostic utility for individuals with operable oral cavity squamous cell carcinomas (OSCCs). We retrospectively analyzed data from 288 patients who were given a diagnosis of primary OSCC from January 2008 to December 2017. The SCI value was derived by multiplying the serum squamous cell carcinoma antigen and neutrophil-to-lymphocyte ratio values. We appraised the associations of the SCI with survival outcomes by performing Cox proportional hazards and Kaplan-Meier analyses. We constructed a nomogram for survival predictions by incorporating independent prognostic factors in a multivariable analysis. By executing a receiver operating characteristic curve analysis, we identified the SCI cutoff to be 3.45, and 188 and 100 patients had SCI values of <3.45 and ≥3.45, respectively. The patients with a high SCI (≥3.45) were associated with worse disease-free survival and overall survival than those with a low SCI (<3.45). An elevated preoperative SCI (≥3.45) predicted adverse overall survival (hazard ratio [HR] = 2.378; p < 0.002) and disease-free survival (HR = 2.219; p < 0.001). The SCI-based nomogram accurately predicted overall survival (concordance index: 0.779). Our findings indicate that SCI is a valuable biomarker that is highly associated with patient survival outcomes in OSCC.

Photoelectrochemical immunoassay of squamous cell carcinoma antigen based on CuO/nitrogen-doped porous carbon-ZnO biolabeling and a type-II In2O3/AgBiS2 heterojunction.

AgBiS2 was hydrothermally synthesized, In2O3 was synthesized by hydrothermal method and calcination, and the type-II In2O3/AgBiS2 heterojunction material of an optimized composition ratio was cast-coated on a fluorine-doped tin oxide (FTO) slice to fabricate an In2O3/AgBiS2/FTO photoanode. The signal-attenuated photoelectrochemistry sandwich immunoassay of squamous cell carcinoma antigen (SCCA) was realized on this photoanode, on the basis of a bovine serum albumin/secondary antibody/CuO nanoparticles/nitrogen-doped porous carbon-ZnO bionanocomposite that can competitively absorb light and deplete the electron donor ascorbic acid as well as show the steric hindrance and p-n quenching effects. Under the optimized conditions (e.g.,at a bias of 0 V vs. SCE), the photocurrent was linear with the common logarithm of SCCA concentration from 2.00 pg mL-1 to 50.0 ng mL-1, with a limit of detection (LOD) of 0.62 pg mL-1 (S/N = 3). The immunoassay of SCCA in human serum samples gave satisfactory recovery (92.0~103%) and relative standard deviation (5.1~7.8%) results.

Role of squamous cell carcinoma antigen in prognostication, monitoring of treatment response, and surveillance of locally advanced cervical carcinoma.

Squamous cell carcinoma antigen (SCC Ag) is a sub-fraction of the tumor antigen TA-4, first isolated by Kato and Torigoe, the most commonly used tumor marker in cervical cancer. It can be used as a serum marker to detect residual disease, early local recurrence, or distant metastasis in locally advanced cervical cancer even before the clinical symptoms of recurrence or metastasis. Between January 2018 and August 2018, 30 patients with squamous cell carcinoma cervix (FIGO) stages IB2-IVA, who received concurrent chemoradiation, followed by brachytherapy, were included in the study. Serum SCC Ag levels were collected at four time points during the course of the treatment, and their correlation with tumor and treatment factors were analyzed. As the FIGO stage increases, mean pre-treatment SCC Ag also increases. Node-positive patients had higher pre-treatment SCC Ag as compared to those who were negative (P = 0.05). There was a statistically significant decreasing trend in the mean SCC Ag at the end of EBRT (P = 0.015). After completion of treatment, 78% had a complete response, 8% had a partial response, and 14% had progressive disease with statistically significant elevation of SCC Ag at 6 weeks of follow-up (P = 0.01). Patients who progressed or had the residual disease at follow-up were found to have high pre-treatment SCC Ag values. SCC Ag can be potentially used as a reference indicator of biological behavior of cervical cancer, to monitor the treatment response, and as a prognostic marker, especially in those with node-positive disease.

Abstract 2374: Squamous cell carcinoma antigen regulates macrophage polarization, contributing to inhibition of T cell activity in cervical cancer chemo-radiotherapy

Abstract Chemoradiation therapy (CRT) is the standard treatment for locally advanced cervical cancer. Anti-tumor T cell response is critical for immunogenic cell death and tumor regression enabled by CRT. Squamous cell carcinoma antigen (SCCA) is highly expressed in cervical tumors and passively released from tumor cells. Patients with elevated serum SCCA often showed radioresistance and recurrence. Despite its prognostic value, little is known about the function of extracellular SCCA. We analyzed SCCA-associated immune landscape using RNAseq from 20 cervical matched tumor biopsy pairs collected prior to (pre-) and 3 weeks into (mid-) CRT. Patients with low pretreatment SCCA (&amp;lt;6 ng/ml, SCCA/L) and high SCCA (≥6ng/ml, SCCA/H) showed decreased CD4/CD8 T cells at mid-CRT, with a more significant decrease in SCCA/H patients. This corresponded to significantly reduced expression of T-cell trafficking chemokine CXCL9/10 during CRT, particularly in SCCA/H patients. Interestingly, granzyme B (GZMB) and interferon-γ (IFNγ), associated with T-cell cytotoxicity, were increased in 6 of the 10 SCCA/L patients, compared to 1 and 2 of the 10 SCCA/H patients with increased GZMB and IFNγ respectively. Another RNAseq cohort of 66 pre-CRT tumor biopsies also showed significantly higher LAG3 and CTLA4 expression in SCCA/H than SCCA/L patients. In vitro stimulation of human PBMC with CD3/28 antibody in the presence of SCCA1 protein resulted in inhibition of T cell proliferation and decreased cytotoxicity. However, when SCCA1 was incubated with purified CD3 T cells, no inhibition in T cell activity was observed, suggesting the involvement of myeloid cells in SCCA1 mediated T cell activity. To investigate the effect of SCCA1 on myeloid cells, we isolated human CD14+ monocytes, incubated with SCCA1, and found improved survival of CD14+ HLADRlo/neg monocytes. THP1 monocytes, possessed polarizing ability, were differentiated into M1/M2 macrophage with the supplement of SCCA1 during the polarization. The result showed that SCCA1 promoted M2 macrophage phenotypes, including increased M2 marker (CD209), PD-L1 expression, M2-associated cytokines (IL10, CCL18), and M2 polarizing signaling (STAT3 phosphorylation and Myc expression). Macrophages isolated from murine tumors with high SCCA1 expression demonstrated increased suppression on T cell activity in co-culture functional assays. Furthermore, tissue microarray from cervical cancer patients showed that high SCCA was associated with increased infiltration of CD11b+ myeloid cells and CD68+ macrophages in tumors. Overall, we concluded that SCCA promoted M2 polarization and macrophage infiltration, which may contribute to T cell exhaustion, leading to poor survival. Thus, therapeutic targeting of extracellular SCCA should be considered to improve treatment outcomes. Citation Format: Liyun Chen, Victoria Shi, Matthew Inkman, Jin Zhang, Pippa Cosper, Julie K. Schwarz, Stephanie Markovina. Squamous cell carcinoma antigen regulates macrophage polarization, contributing to inhibition of T cell activity in cervical cancer chemo-radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2374.

Abstract 466: A potential pro-oncogenic role of SERPINB4 in melanoma

Abstract Despite recent therapeutic advancements, melanoma remains one of the deadliest forms of skin cancer. Melanoma metastasis and recurrence is associated with the existence of heterogeneous cell populations within tumors that have the ability to both initiate metastatic programs and bypass immune recognition. Tumor cells achieve immune evasion by interfering with immune signaling to limit immune cell infiltration, allowing tumor cell proliferation and growth. SERPINB4 (Squamous Cell Carcinoma Antigen 2 or SCCA2), a serine protease inhibitor, has been shown to regulate the host immune response against tumor cells by inhibiting immune cell activity. Interestingly, certain cancer cell types have been reported to overexpress SERPINB4. However, the expression profile and the functional significance of SERPINB4 in melanoma is not known. In this study, employing ‘The Cancer Genome Atlas’ (TCGA), we found that SERPINB4 is overexpressed and significantly associated with lower overall survival in patients with melanoma. Next, employing a panel of human melanoma cell lines, we demonstrated that SERPINB4 is overexpressed in melanoma cells when compared to normal human melanocytes. In addition, CRISPR knockout of SERPINB4 in high-SERPINB4-expressing A375 melanoma cells resulted in a significant decrease in proliferation of melanoma cells in comparison to control cells. Conversely, forced overexpression of SERPINB4 in low-SERPINB4-expressing SK-MEL-2 and SK-MEL-28 melanoma cells significantly increased melanoma cell proliferation. Moreover, RT-qPCR analyses suggested that SERPINB4 overexpression significantly increased, while its knockout significantly decreased epithelial-mesenchymal transition (EMT) markers (N-cadherin, β-catenin, Snail and Zeb1) in melanoma cells. Additionally, SERPINB4 manipulation significantly modulated the expression of genes involved in antigen-presentation (MHC Class I molecules, HLA-A, -B, and -C) in melanoma cells. Taken together, our data suggested a potential oncogenic role of SERPINB4 in melanoma. Our study also suggested that SERPINB4 might be a promising therapeutic target for melanoma. Indeed, additional in vitro mechanistic and in vivo studies are needed to firmly establish the mechanism and therapeutic potential of SERPINB4 for melanoma management. Citation Format: Gagan Chhabra, Carl A. Shirley, Rachel K. Robarge, Hassan A. Rizvi, Mary A. Ndiaye, Nihal Ahmad. A potential pro-oncogenic role of SERPINB4 in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 466.

Abstract 6225: SERPINB3 promotes the aggressive basal-like/squamous subtype and correlates with poor prognosis in pancreatic ductal adenocarcinoma through metabolic reprogramming

Abstract In this study, we aimed to find genes with a key function in the development of molecular subtypes in pancreatic ductal adenocarcinoma (PDAC). Through transcriptome analysis, we discovered that the endogenous serine/cysteine proteinase inhibitor SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) was distinctively upregulated in the basal-like/squamous subtype, known as an aggressive subtype, and this upregulation associated with decreased patient survival in both a test (N=123) and a validation cohort (N=84). In additional investigations of the tumor metabolome and transcriptome using PDAC patient tumors and cell lines, SERPINB3 and the basal-like/squamous subtype showed a robust relationship with upregulated levels of amino acids (e.g., hydroxyproline) whereas SERPINB3 promoted a gene signature indicative of the basal-like/squamous subtype. Additional mechanistic studies revealed that SERPINB3 and hydroxyproline promoted the migration/invasion of PDAC cells. Moreover, SERPINB3 also promoted metastasis in an orthotopic mouse model of PDAC through stromal factors that increased tumor microvessel density. To conclude, inhibiting SERPINB3 function may attenuate disease progression of the basal-like/squamous subtype in PDAC through changes to the tumor stroma and tumor metabolism. Citation Format: Yuuki Ohara, Wei Tang, Liu Huaitian, Shouhui Yang, Peijun He, Helen Cawley, Paloma Valenzuela, Lin Zhang, Jochen Gaedcke, B. Michael Ghadimi, Matthias M. Gaida, Frank Bergmann, H. Richard Alexander, Nader Hanna, Stefan Ambs, S. Perwez Hussain. SERPINB3 promotes the aggressive basal-like/squamous subtype and correlates with poor prognosis in pancreatic ductal adenocarcinoma through metabolic reprogramming [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6225.