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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND/AIM: 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). PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Unveiling the Potential of Serum MiR-483-5p: A Promising Diagnostic and Prognostic Biomarker in OLP and OSCC Patients by In silico Analysis of Differential Gene Expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression. METHODS: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients. RESULTS: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes. CONCLUSION: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.

Evaluation of Platelet Parameters in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma in a Background of Oral Submucous Fibrosis.

CONTEXT: The role of platelet parameters as markers of inflammation in various diseases is now in limelight. The interaction between cancer cells and platelets is a well-established phenomenon. Oral submucous fibrosis (OSMF) is a premalignant disorder with a malignant transformation rate of 2-8%. This study aimed to evaluate platelet parameters in OSMF and oral squamous cell carcinoma (OSCC) in the background of OSMF. This cross-sectional study was performed using secondary data retrieved between January 2019 and December 2019 in the Department of Oral Pathology and the Hematology Laboratory. METHODS AND MATERIALS: The data retrieved included 44 histopathologically proven OSCC in a background of OSMF (group III) and 36 OSMF (group II). The haematological parameters of these selected cases were retrieved from the Sysmex XN-1000 automated hematology analyser database. A control group (group I) comprises 50 subjects with normal (negative/unflagged) haematological parameters. All data were statistically analysed using SPSS 20.0. The significance level of tests was set at 5%. RESULTS: The mean platelet volume (MPV) (9.60 [±0.95] P < 0.001), platelet distribution width (PDW) (10.45 [±1.9], P < 0.001), platelet large cell ratio (PLCR) (21.70 [±7.98], P < 0.001), and the ratio of mean platelet volume to total platelet count (MPV/PLT) (0.03 [0.01], P < 0.001) were lower in group III when compared to the other two groups. CONCLUSIONS: Platelet parameters may be used as indices in the OSCC in the background of OSMF. However, large-scale prospective studies are necessary to evaluate the utility of these parameters during the malignant transformation of OSMF, thereby encouraging prompt treatment to prevent morbidity and mortality.

On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial.

BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. METHODS: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. RESULTS: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. CONCLUSION: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03668496.

Comparison of circulating DNA in malignant neoplasia from diverse locations: Investigating a diagnostic role.

CONTEXT: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage. DESIGN: Serum samples were collected from treatment naïve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis. RESULTS: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases. CONCLUSION: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.

Prognostic value of tumor measurement parameters and SCC-Ag changes in patients with locally-advanced cervical cancer.

OBJECTIVE: To investigate the prognostic relevance of specific measurement parameters such as tumor diameter, tumor volume, tumor volume reduction rate (TVRR), and changes in the squamous cell carcinoma antigen (SCC-Ag) level in patients with locally-advanced cervical cancer (LACC) undergoing concurrent radiotherapy and chemotherapy. METHODS: This was a retrospective study of 203 patients with stage IIA-IVA cervical squamous cell carcinoma who were newly diagnosed at our hospital between January 2011 and March 2015. Clinical data and pre-and post-treatment imaging information were collected and each parameter was calculated using 3DSlicer software. The pre/post-treatment tumor diameter (TDpre/post), tumor volume (TVpre/post), SCC-Ag (SCCpre/post), and TVRR, SCC-Ag reduction rate (SCCRR) were analyzed and their prognostic relevance evaluated. RESULTS: The median follow-up was 69 months. The 5-year overall survival (OS) and disease progression-free survival (PFS) rates were 69.5% and 64.5%, respectively. On univariate analysis, TDpre/post, TVpre/post, TVRR, SCCpre/post and SCCRR showed significant association with OS and PFS (P < 0.05). On multivariate analysis, TDpre [Hazard ratio (HR) = 0.373, P = 0.028], TDpost (HR = 0.376, P = 0.003) and SCCpost (HR = 0.374, P = 0.001) were independent predictors of OS. TVRR (HR = 2.998, P < 0.001), SCCpre (HR = 0.563, P = 0.041), and SCCpost (HR = 0.253, P < 0.001) were independent predictors of PFS. Tumor measurement parameters showed a positive correlation with SCC-Ag (P < 0.05). CONCLUSION: TDpre/post, TVpre/post, TVRR, SCCpre/post, and SCCRR were prognostic factors in LACC. TDpre/post and SCCpost showed the most significant prognostic value. TVRR and SCCpre/post were closely related to disease progression. Further studies should investigate the correlation between measurement parameters of tumor and SCC-Ag.

Detection of circulating tumor cells as therapeutic markers in patients with penile squamous cell carcinoma: A preliminary study.

BACKGROUND: This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS: CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS: CTCs were found in all PSCC blood samples but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION: Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for noninvasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.

Circulating C-reactive protein increases lung cancer risk: Results from a prospective cohort of UK Biobank.

Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; Pnonadjusted  = .003, Padjusted  = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers.

Heme Sequestration Effectively Suppresses the Development and Progression of Both Lung Adenocarcinoma and Squamous Cell Carcinoma.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two most common subtypes of lung cancer. Here, to identify new, targetable molecular properties of both subtypes, we monitored changes in the levels of heme- and oxidative phosphorylation (OXPHOS)-related proteins during lung tumorigenesis. Heme is a central molecule for oxidative metabolism and ATP generation via OXPHOS. Notably, both lung ADC and SCC tumors can be induced in the genetically engineered KLLuc mouse model harboring the G12D Kras mutation and a conditional Lkb1 knockout. We found that the levels of the rate-limiting heme synthesis enzyme ALAS1 and uptake protein SLC48A1, along with OXPHOS complex subunits, progressively increased as lung tumorigenesis advanced. Our data demonstrated that elevated levels of heme- and OXPHOS-related proteins were associated with both ADC and SCC. Importantly, treatment of KLLuc mice with a heme-sequestering protein, HeSP2, that inhibits heme uptake in tumor cells effectively arrested lung tumor progression, and both ADC and SCC tumors were strongly suppressed. Additionally, HeSP2 effectively suppressed the growth of both SCC and ADC tumor xenografts in NOD/SCID mice. Further analyses indicated that HeSP2 effectively diminished OXPHOS in both ADC and SCC, reduced angiogenesis, alleviated tumor hypoxia, and suppressed cell proliferation. These results show that the advancing of lung tumorigenesis requires progressive increase in cellular heme synthesis and uptake, leading to intensified OXPHOS activity and ATP generation and promoting aggressive tumorigenic functions. IMPLICATIONS: Heme sequestration is an effective strategy for the suppression of both ADC and SCC tumor initiation and development.

Molecular profiling and utility of cell-free DNA in nonsmall carcinoma of the lung: Study in a tertiary care hospital.

BACKGROUND: Lung carcinoma accounts to the most common cause of cancer globally. Optimal management of nonsmall cell lung carcinoma (NSCLC) requires prognostic biomarkers that help in targeted therapy and identification of tumor subsets with a distinctive molecular profile that can foretell response to therapy. Quantitative analysis of circulating cell-free DNA is considered as a possible aid for lung cancer screening. AIMS AND OBJECTIVES: The main aim of our study was detection of the clinicopathological spectrum of NSCLC, immunohistochemical (IHC) study of lung adenocarcinoma with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and molecular expression of EGFR mutation using Formalin fixed paraffin embedded tissue (FFPE) and cell-free DNA (cfDNA) from blood samples. MATERIALS AND METHODS: It was a prospective and observational study conducted in the Department of Pathology in association with the Department of Chest Medicine in a tertiary care hospital for 18 months, done on 50 patients. Histological subtyping of lung carcinomas was done, followed by IHC analysis using P40, thyroid transcription factor (TTF1), EGFR, and ALK. Molecular analysis for EGFR mutation was done using FFPE and cfDNA from the patient's blood samples. RESULTS AND ANALYSIS: On histological subtyping, majority (66%) of the cases were found to be adenocarcinoma. All adenocarcinoma (66%) cases show TTF1 positivity and all squamous cell carcinoma (32%) cases show P40 positivity. All the ALK-positive (6%) cases were never smokers and histologically diagnosed as adenocarcinoma. About 58% of the NSCLC cases were found to be EGFR IHC positive. Formalin-fixed paraffin tissue (FFPE) showed EGFR mutation in 32% cases, of which majority were deletion (19, 28%) and rest (4%) of the cases involving mutation in exon 21. From cfDNA, mutations were noticed in 16% of the cases where majority involved deletion 19 (12%), whereas the rest of the cases were positive for missense mutation in exon 21 of the EGFR gene (2%) and compound heterozygous mutation involving deletion 19 and missense mutation for exon 21 (2%). On correlation of EGFR mutation studies from FFPE with that of cfDNA analysis, the study was statistically significant (P = 0.000). CONCLUSION: This study reports clinicopathological, immunochemical, and molecular analysis of EGFR among NSCLC cases. EGFR mutation detection from cfDNA has its advantage of being a noninvasive technique to avoid rebiopsy in cases of the progressive disease to detect resistance to a drug and emergence of a newer mutation. Mutation detection from FFPE samples still remains the gold standard for targeted therapy using EGFR tyrosine kinase inhibitors. ALK rearrangement detection using IHC serves as an adjunct to EGFR diagnosis.

Cell-free DNA and circulating tumor cell kinetics in a pre-clinical head and neck Cancer model undergoing radiation therapy.

BACKGROUND: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. METHODS: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. RESULTS: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.

The Role of Serum Tumor Markers in Follow-up After Surgical Treatment of Malignant Lung Tumors.

AIM: The aim of this study was to evaluate the utility of selected tumor markers for the detection of lung cancer recurrence during follow-up. PATIENTS AND METHODS: The study group consisted of 109 patients and 109 healthy controls. The following biomarkers were selected: Carcinoembryonic antigen; cytokeratin fragment 19; neuron-specific enolase; tissue polypeptide-specific antigen; cytokeratin fragments 8, 18 and 19; insulin-like growth factor 1; pro-gastrin-releasing peptide; and 25-hydroxyvitamin D. The biomarkers were assessed individually or using a multivariate analysis. RESULTS: Carcinoembryonic antigen [area under the receiver operating characteristics curve (AUC)=0.6857, p<0.0001] and cytokeratin fragment 19 (AUC=0.6882, p<0.0001) proved best in detecting relapse. The multivariate model indicated insulin-like growth factor 1 (p=0.0006, AUC=0.6225) as the third most useful biomarker. The multivariate model using these three markers achieved the best AUC value of 0.7730 (p=0.0050). CONCLUSION: We demonstrated that carcinoembryonic antigen and cytokeratin fragment 19 play a key role in the detection of lung cancer recurrence. A multivariate approach can increase the effectiveness of detection.

The role of haematological parameters in predicting the response to radical chemoradiotherapy in patients with anal squamous cell cancer.

BACKGROUND: Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20-30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. PATIENTS AND METHODS: This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. RESULTS: A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). CONCLUSIONS: Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.

Clinical significance of detecting HDL and miR-103 levels in lung carcinoma patients.

PURPOSE: To elucidate the clinical significance of microRNA (miR)-103 and HDL in influencing pathological features in lung carcinoma, and to predict chemotherapy efficacy of lung carcinoma according to the expression changes of miR-103 and HDL before and after chemotherapy. METHODS: Serum levels of miR-103 and HDL were detected in lung carcinoma patients (n=60) and healthy subjects (n=60) by qRT-PCR. The correlation between miR-103 and HDL in serum samples of lung carcinoma patients was assessed. In addition, their influence on pathological features in lung carcinoma were analyzed. Changes in HDL and miR-103 levels in lung carcinoma patients based on their therapeutic efficacy were evaluated and analyzed. RESULTS: Serum levels of miR-103 and HDL were lower in lung carcinoma patients than those of healthy subjects. MiR-103 level was correlated to that of HDL in serum samples of lung carcinoma patients. HDL level was correlated to smoking, TNM staging and presence of lymph node metastasis of lung carcinoma, while miR-103 level was correlated to TNM staging and presence of lymph node metastasis of lung carcinoma. Serum levels of miR-103 and HDL were significantly enhanced in lung carcinoma patients achieving PR after chemotherapy (p<0.05). No significant differences in miR-103 and HDL levels before and after chemotherapy were observed in lung carcinoma patients achieving stable disease (SD) or progressive disease (PD). CONCLUSION: MiR-103 and HDL are involved in the progression of lung carcinoma. Their expression changes after chemotherapy can be utilized for predicting therapeutic efficacy and prognosis in lung carcinoma patients.

Diagnostic value of serum tumor-associated autoantibodies in esophageal cancer.

Aim: To explore the application value of serum autoantibodies in the early diagnosis of esophageal cancer. Materials & methods: A total of 130 patients with esophageal cancer and 110 controls were included and tested by ELISA. Results: According to the receiver operating characteristic curve, total sensitivity is 83.08%, total specificity is 72.73%. A nomogram was established based on the positive judgment standard, the area under the receiver operating characteristic curve was calculated to be 0.880 after verification with the calibration curve. A 2-week follow-up analysis found compared with the preoperative control, the postoperative model integral value will significantly decrease. Conclusion: The combination of serum autoantibody groups has certain clinical application value in the early diagnosis of esophageal cancer and can be used as an auxiliary index for early diagnosis.

Cross-Sectional Study to Establish the Utility of Serum Tumor Markers in the Diagnosis of Lung Cancer.

BACKGROUND: Reliable blood markers for aiding lung cancer (LC) diagnosis and differentiating LC from tuberculosis are lacking in India. METHODOLOGY: In this single-centre, cross-sectional, real-world study, serum levels of 5 TMs (CEA, CYFRA 21-1, SCC, ProGRP, NSE) were measured from consented patients with suspicious lung nodules who were candidates for biopsy, and also from healthy controls. TM level measurement was done through electrochemiluminescent immunoassay, followed by histological diagnosis on the biopsied specimen. Using package insert cut-offs, sensitivity and specificity of the 5 TMs were evaluated individually and in combination. Using receiver operating characteristic (ROC) curves of individual TMs, the ability of CEA, CYFRA 21-1, and ProGRP taken together was evaluated for its ability to differentiate LC from no-LC. RESULTS: Out of 178 subjects, 160 had LC (147 NSCLC; 13 SCLC). NSCLC patients had higher median values of CYFRA 21-1 and SCC; SCLC patients had higher median values of CEA, NSE, and ProGRP. Adenocarcinoma-NSCLC patients had higher median values of CEA, CYFRA 21-1, NSE, and ProGRP; squamous-NSCLC patients had higher median value of SCC. For differentiating LC from no-LC, the combination of all 5 TMs (sensitivity:97.5%, specificity:33.3%) and combination of CEA, CYFRA 21-1 and ProGRP (sensitivity:91.3%, specificity:88.9%) were found suitable. CONCLUSION: Combination of all 5 TMs, and combination of CEA, CYFRA 21-1, and ProGRP represents an easy and non-invasive method for aid in LC diagnosis that does not require technical expertise. TM evaluation can also supplement histological diagnosis of LC. 
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Influence of the Levels of Arsenic, Cadmium, Mercury and Lead on Overall Survival in Lung Cancer.

The effects of heavy metals on cancer risk have been widely studied in recent decades, but there is limited data on the effects of these elements on cancer survival. In this research, we examined whether blood concentrations of the heavy metals arsenic, cadmium, mercury and lead were associated with the overall survival of lung cancer patients. The study group consisted of 336 patients with lung cancer who were prospectively observed. Blood concentrations of heavy metals were measured to study the relationship between their levels and overall survival using Cox proportional hazards analysis. The hazard ratio of death from all causes was 0.99 (p = 0.94) for arsenic, 1.37 (p = 0.15) for cadmium, 1.55 (p = 0.04) for mercury, and 1.18 (p = 0.47) for lead in patients from the lowest concentration quartile, compared with those in the highest quartile. Among the patients with stage IA disease, this relationship was statistically significant (HR = 7.36; p < 0.01) for cadmium levels in the highest quartile (>1.97-7.77 µg/L) compared to quartile I (0.23-0.57 µg/L, reference). This study revealed that low blood cadmium levels <1.47 µg/L are probably associated with improved overall survival in treated patients with stage IA disease.

Predictive value of preoperative serum squamous cell carcinoma antigen level for lymph node metastasis in early-stage cervical squamous cell carcinoma.

ABSTRACT: To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ2 = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ2 = 14.339, P < .001), LVSI (χ2 = 12.866, P  < .001), parametrial involvement (χ2 = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.