Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.

A Novel Model Using Serum Thymidine Kinase 1 and Low-dose Computed Tomography Parameters to Predict Three-year Lung Cancer Risk in People with Pulmonary Nodules: A Retrospective Study.

This study was designed to develop a model of serum thymidine kinase 1 protein (STK1p) concentration in combination with low-dose computed tomography (LDCT) to predict the risk of benign pulmonary nodules progressing into lung cancer within three years in a large screening population. The study included a retrospective cohort of 6,841 individuals aged > 30 years who had LDCT-detected pulmonary nodules, but no cancer history or baseline cancer. The outcome was a lung cancer diagnosis recorded within three years after the first detection of pulmonary nodules. The adaptive least absolute shrinkage and selection operator was used to select candidate predictors and fit a logistic model. The model was validated internally by examining discrimination (area under the receiver operating characteristic curve (AUC), calibration (calibration plot)) and net benefit. A web application was developed based on the model. The results showed that the proportion of incident lung cancer cases was 0.79% (n=52). Predictors selected for the model were STK1p and three LDCT parameters (nodule size, type, and count). The AUC of the model was 0.91 (95% confidence interval (CI): 0.86, 0.96). The model had satisfactory discrimination at internal validation (AUC: 0.90 (0.84, 0.96)) and in subgroups (AUC=0.69-0.93). The high-risk group identified by the model exhibited a significantly higher three-year lung cancer risk than the low-risk group (odds ratio (OR): 66.03 (95% CI: 30.49, 162.98)). We concluded that the novel model of STK1p and LDCT parameters together can be used to accurately predict the three-year risk of lung cancer in people with pulmonary nodules.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

Development of a Novel Recombinant Full-Length IgY Monoclonal Antibody against Human Thymidine Kinase 1 for Automatic Chemiluminescence Analysis on a Sandwich Biotin-Streptavidin Platform for Early Tumour Discovery.

Serum thymidine kinase 1 protein (STK1p) concentration has been used successfully as a reliable proliferating serum biomarker in early tumour discovery and clinical settings. It is detected by an enhanced chemiluminescence (ECL) dot blot assay with the biotin-streptavidin (BSA) platform (a gold standard) based on chicken anti-human thymidine kinase 1 IgY polyclonal antibody (hTK1-IgY-pAb). However, ECL dot blotting is a semiautomatic method that has been limited to large-scale applications due to the differences among batches of antibodies from individual hens, and the skill level of operation technicians sometimes results in unstable STK1p values. Therefore, a highly stable recombinant chicken full-length IgY monoclonal antibody in combination with a fully automated sandwich biotin-streptavidin (sandwich-BSA) platform was developed. Hens were immunized with 31-peptide, a key sequence of human TK1 (hTK1), before constructing an immune phage display scFv library. Finally, a recombinant full-length IgY monoclonal antibody (hTK1-IgY-rmAb#5) with high-affinity binding with human recombinant TK1 (rhTK1) (3.95 × 10-10 mol/L), high sensitivity with hTK1 calibrators (slope of linear curve: 89.98), and high specificity with low/elevated STK1p (r ≈ 0.92-0.963) was identified. hTK1-IgY-rmAb#5 showed a specific immune response with thymidine kinase 1 (TK1) in TK1-positive/negative cell lysates by Western blotting and immunohistochemistry (IHC) in normal and cancer tissues. In particular, the detection of TK1 serum samples from health centres showed a high coincidence rate (r = 0.988, n = 90) between hTK1-IgY-rmAb#5 and hTK1-IgY-pAb and between the semiautomatic ECL dot blot BSA platform and the novel automatic chemiluminescence sandwich-BSA platform (r = 0.857, n = 292). hTK1-IgY-rmAb#5 is stable and highly sensitive for detecting the lowest STK1p value at 0.01 pmol/L (pM). The accuracy is high (SD < 2.5%) between different batches. It is easy to use the novel hTK1-IgY-rmAb#5 on a new automatic chemiluminescence sandwich-BSA platform. It will be beneficial for large-scale health screenings.

Is serum thymidine kinase 1 a prognostic biomarker in primary tumor location of colorectal carcinomas?

AIM: To assess whether serum thymidine kinase 1 (STK1p), CEA and CA19.9 can be used as prognostic biomarkers in the primary tumor location (PTL) of colorectal carcinoma (CRC). Additional clinical factors of TNM stage, pathological grade, age and sex were also included. METHODS: STK1p was determined by an ECL-dot-blot assay, and CEA/CA19.9 was determined by an automatic electrochemiluminescence analyzer in a retrospective presurgery of right-colon carcinoma (R-CC, n = 90), left-colon carcinoma (L-CC, n = 128) and rectal carcinoma (RC, n = 270). Prognostic factors were evaluated by COX and overall survival (OS). RESULTS: The multivariate-COX and OS in relation to the prognostic factors of PTL in CRC were different and complex. An elevated STK1p value was significantly associated with poor OS in RC (P = 0.002) and L-CC (P = 0.037) but not in R-CC (P > 0.05). Elevated CEA (P≈.000) and CA19.9 (P≈.000) were significantly associated with poor OS in RC but not in L-CC and R-CC. Multivariate-COX showed that STK1p (P = 0.02, HR = 1.779, 95%CI 1.30-7.582), CEA (P = 0.001, HR = 2.052, 95%CI 1.320-3.189), CA19.9 (P≈.000, HR = 2.574, 95%CI 1.592-4.162) and TNM-stage (P≈.000, HR = 2.368, 95%CI 1.518-3.694) were independent prognostic factors in RC, while TNM-stage was an independent prognostic factor only in R-CC (P = 0.011, HR = 3.139, 95% CI 1.30-7.582) and L-CC (P≈.000, HR = 4.168, 95%CI 1.980-8.852). Moreover, elevated STK1p was significantly more sensitive (P < .001) for predicting mortality than CEA and CA19.9. No correlation was found between STK1p, CEA or AFP. CONCLUSION: Combining TNM stage and suitable biomarkers, STK1p provides further reliable information on the survival of PTL of CRC.

Concentration of human thymidine kinase 1 discover invisible malignant human tumours.

Early discover of risk progression of invisible carcinomas is important for a prerequisite successful treatment. Here, we investigated whether concentration of human thymidine kinase 1 (HTK1) discover invisible malignant human tumours. The HTK1 concentration of tumour cellular based on HTK1 IgY-polyclonal-antibody (HTK1-IgY-pAb) was determined by using a novel automatic chemiluminescence analyser with sandwich biotin-streptavidin (SBSA) platform. Minimum number of cells able to be detected by this technology used cells with low and high concentration of HTK1. The limit visibility by tumour imaging is approximately 1 mm in diameter, corresponding to approximately 109 cells with a cell diameter of 1 µm. Based on a HTK1 standard curve and a molecular weight of HTK1 of 96 kD, the HTK1protein (HTK1p) concentration per cell was calculated to be 0.021 pg. Assuming 200 pg in total protein/cell, approximately 50 × 106 growing malignant cells in the body were calculated to releases HTK1 into 5-liter blood. A HTK1 values of 3.914, 0.435 and 0.009 pmol/L corresponds to 10 × 105, 2 × 105 and 1 × 105 growing malignant cells, respectively. The lowest detectable sensitivity of HTK1 is 0.009 pmol/L in 1 × 105 growing malignant cells and 0.01 pmol/L in blood serum, detectable in health screening. Comparing the novel automatic chemiluminescence analyser with the original ECL dot-blot assay using serum HTK1p (health screening, n = 265) showed high correlation (r = 0.8743, P < .000). In conclusion, the novel automatic chemiluminescence analyser with SBSA platform is a reliable method with high accuracy to determine carcinoma invisible.

Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification.

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects.

Introduction: An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methods: The novel N-IgY-pAb and its intranasal spray response against the wild type ("'WH-Human 1") SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray. Results: Seventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121). Discussion and conclusion: We concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and "cocktails" of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.

Serum thymidine kinase 1 protein concentration for predicting early progression and monitoring the response to TACE in hepatocellular carcinomas: a network meta-analysis.

AIM: A meta-analysis was conducted to evaluate the clinical significance of serum thymidine kinase 1 protein concentration (STK1p) in distinguishing between hepatocellular carcinomas (HCC) and non-HCC for predicting early progression and monitoring the response to transarterial chemoembolization in HCC. MATERIALS & METHODS: A total of 24 eligible studies were included, containing 1849 HCC patients and 1069 healthy subjects. RESULTS: The STK1p level significantly increased from normal controls to benign/pre-HCC and HCC (p < 0.0001). STK1p also increased significantly in sub-malignant groups: control being the lowest, followed consecutively by hepatic hemangioma, hepatitis B virus infection and hepatic cirrhosis (p < 0.05). After 1 month of transarterial chemoembolization treatment, STK1p level declined significantly, by 44.4% (p < 0.0001). CONCLUSION: STK1p is a useful prognostic biomarker in HCC.

A meta-analysis of serological thymidine kinase 1 as a marker for colorectal benign and malignant tumor risk assessment.

The present study investigated whether a concentration of serum thymidine kinase 1 (STK1p) could be used to distinguish between healthy individuals, patients with colorectal benign tumors and individuals with colorectal cancer (CRC). The effectiveness of surgery on patients with CRC was monitored. A total of 20 publications containing patients with CRC (n=1,836), patients with colorectal benign tumors (n=774) and healthy controls (n=1,701) were analysed in the present meta-analysis. The publications were collected from PubMed, Embase, CENTRAL, CNKI, Wanfang, VIP and SinoMed databases from January 1, 2009 until August 31, 2019. Articles were analyzed according to sensitivity (Forest plot) and publication bias (Begg's plot, Egger's linear regression) using fixed or random effect models to calculate the weighted mean difference. Study quality was checked using the Newcastle-Ottawa Scale Document Quality Assessment Scale. The meta-analysis followed the PRISMA statement. The results revealed that STK1p significantly distinguished healthy individuals and those with colorectal benign tumors from patients with CRC, and from patients with benign tumors (P<0.000001). STK1p levels also decreased by 40% following surgery (P<0.0001), which corresponded to half-life of ~1 month. The quality of the present study was high and no bias was identified among publication. It was concluded that STK1p was a reliable biomarker for the early detection of benign lesions, which may therefore prevent their future development into colorectal malignancies. STK1p may also be used for the clinical dynamic monitoring of the effectiveness of surgery in patients with CRC. Combining STK1p with colorectal-associated biomarkers, in addition to the determination of tumor stage and grade may therefore be of use.

STK1p as a prognostic biomarker for overall survival in non-small-cell lung carcinoma, based on real-world data.

AIM: A prospective investigation of serum thymidine kinase 1 concentration (STK1p) was performed to evaluate its prognostic value in patients with non-small-cell lung carcinoma (NSCLCs). PATIENTS & METHODS: The STK1p values of 127 patients were determined by an enhanced chemiluminescent dot blot assay. The patients were recruited from March 2011 to December 2017. RESULTS: Kaplan-Meier plot showed that patients with elevated STK1p values had worse overall survival (OS), especially patients of early/middle stages. Multi-variable COX regression showed that STK1p value and combined treatment surgery + chemotherapy were independent prognostic factors for favorable OS. CONCLUSION: STK1p is helpful in predicting OS of early/middle stages (I-IIIA) NSCLCs patients following a nonrandomized individual adapted treatment, but is may be not recommended in advanced stages (IIIB + IV) of NSCLCs.

Serum thymidine kinase 1 is associated with Gleason score of patients with prostate carcinoma.

The aim of the present was to assess whether serum thymidine kinase 1 (STK1) concentration is a useful biomarker for the screening of benign prostatic hyperplasia (BPH) or prostate malignancy. Serum samples were collected from 123 patients with prostate carcinoma prior to surgery, biopsy or androgen deprivation therapy and at 3, 6 and 10 months following the procedure. A total of 205 patients with BPH and 266 healthy controls were also utilized. STK1 concentration and total prostate-specific antigen (PSA) were measured in patient serum by use of commercial assays. The pathological specimens (obtained from surgery or biopsy) were assessed according to Gleason scores (GS). STK1 concentration and total PSA were significantly higher in patients with prostate carcinoma compared with patients with BPH and healthy individuals. Furthermore, STK1 concentration was associated with Gleason score, while total PSA was not. However, no association was identified between STK1 concentration and total serum PSA. A receiver operating characteristic analysis was performed on STK1 concentrations among patients with prostate carcinoma. The results demonstrated that the sensitivity and specificity were high, with an area under the curve (AUC) of 0.97. Although the sensitivity and specificity of total PSA were also high, the AUC value was relatively low (0.74). The results indicated that STK1 concentration is a more reliable prognostic biomarker than total PSA in respect to the GS system. Additionally, since STK1 concentration is associated with Gleason score, the use of biopsies to determine Gleason score may be replaced to some extent by the STK1 concentration test, thus reducing the discomfort of patients from which biopsies are obtained.

Serum 8-Oxo-dG as a Predictor of Sensitivity and Outcome of Radiotherapy and Chemotherapy of Upper Gastrointestinal Tumours.

The level of oxidative stress is important in the initiation and progression of various age-related diseases, such as cancer. The level of oxidative stress may also play a significant role in cancer patients' response to treatment. We aimed to investigate whether serum 8-oxo-dG as a marker of oxidative stress is a predictor of tumour response. We used modified ELISA with a two-step filtration to analyse 8-oxo-dG in serum. The relationship between 8-oxo-dG levels, tumour response, and toxicity was studied in 19 oesophageal cancer patients who received radiotherapy and 16 gastric cancer patients who received chemotherapy. In the radiotherapy and the merged radio- and chemotherapy groups, the baseline levels of 8-oxo-dG were significantly lower in responder patients than in nonresponder patients and the increments after treatment were greater. In comparison with patients whose serum 8-oxo-dG levels decrease after treatment, patients with increasing levels had a longer median "progression-free survival." Our results, although preliminary, suggest that serum levels of 8-oxo-dG may potentially be used to predict the sensitivity and outcome of radiotherapy and chemotherapy of upper gastrointestinal tumours. Patients with 8-oxo-dG levels that are low prior to treatment and subsequently increase after treatment may be more likely to benefit from the therapy.

Serological TK1 predict pre-cancer in routine health screenings of 56,178 people.

BACKGROUND: People with biomarkers above cut-off values normally have higher risk to develop pre-malignancies and malignancies. OBJECTIVE: Here we investigate if serological TK1 protein (STK1p), AFP, CEA and PSA below cut-off values predict development of pre-cancer. METHODS: The mean values and the concentration distribution of STK1p, AFP, CEA and PSA were determined in a cohort of 56,178 persons participating a health screening group, consist of people with non-tumor diseases, pre-malignancy and diseases associated with the risk process of malignancy. A health disease-free group (n= 428) was selected among the 56,178 participants and used as controls. RESULTS: The STK1p below cut-off value (⩽ 2 pM) showed partly (51.6%) an almost normal concentration distribution and partly (43.9%) an extensive tail in the health screening group, which was not found in the disease-free group. Due to the extensive tail in the distribution, the mean value of STK1p increased significantly (p= 0.0001) from 0.38 ± 0.30 pM in the health disease-free group to 0.69 ± 0.55 pM in the group below the cut-off value. No significantly differences in the concentration distribution and the mean values among gender and ages were observed. On the other hand, there were no difference in the concentration distributions and the mean values of AFP, CEA and PSA between the health disease - free group and the group below cut-off values, as well as between gender and ages. Of interest, the elevated mean value of STK1p of the group below the cut-off value was correlated to pre-malignancy and diseases associated with the risk process of malignancy in liver and prostate. No such correlations were found with AFP, CEA and PSA. CONCLUSION: STK1p is a potential proliferating biomarker for early discover of persons in the risk to develop or already have pre-malignancies or diseases associated with the risk process of malignancy.

The Half-Life of Serum Thymidine Kinase 1 Concentration Is an Important Tool for Monitoring Surgical Response in Patients with Lung Cancer: A Meta-Analysis.

AIMS: In this meta-analysis, we evaluated the usefulness of serum thymidine kinase 1 concentration (STK1c) for monitoring the outcome of extensive open surgery in patients with lung cancer. We also compared STK1c between a healthy population and patients with benign and malignant lung tumors to assess its potential value for early detection of lung cancer and for distinguishing between benign lung disease and malignant cancer. MATERIALS AND METHODS: Related studies were retrieved from publications in PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang databases, and Internet searches. Correlation was evaluated using weighted mean difference. Fixed or random effect models were selected for data analyses based on heterogeneity tested with the chi-square test. Publication bias was assessed using a funnel plot and Egger's test. RESULTS: Twenty studies were selected for analysis, which showed that STK1c was significantly (p < 0.00001) reduced by 41.7% 1 month after extensive open surgery, approximately corresponding to an STK1c half-life of 1 month. STK1c levels were significantly higher in lung cancer patients than in healthy persons (p < 0.00001) or in patients with benign lung disease (p < 0.00001). There was also a significant difference in STK1c between patients with benign and malignant lung disease (p < 0.0001). CONCLUSIONS: The half-life of STK1c may be an important tool in the clinical evaluation of surgical response in patients with lung cancer. STK1c may also be beneficial in the early detection of lung cancer.

Thymidine kinase 1 expression in ovarian serous adenocarcinoma is superior to Ki-67: A new prognostic biomarker.

Cancer is a disease with abnormally proliferating cells and therefore proliferation rate is an important index for assessing tumour growth. Ki-67 is a commonly used proliferation marker considered to be an unfavourable prognostic marker in some tumors, while Thymidine kinase 1 (TK1) is an interesting proliferation marker because its levels are highly dependent on the growth stage of cells. To define the immunohistochemistry (IHC) expression of the TK1 in patients with ovarian serous adenocarcinoma and establish its potential role as a new biomarker for progressive disease, we analyzed the expression patterns of TK1 and Ki-67 in 109 patients with ovarian serous adenocarcinoma. TK1 and Ki-67 expression both showed a statistically significant correlation to MD Anderson Cancer Center (MDACC) grade, but not to age, tumour size, lymph node metastasis or pathological TNM (pTNM) stages. TK1 expression, MDACC grades, pathological stages and lymph node metastasis correlate to relapse incident rate and overall survival, but Ki-67 does not. Although TK1 expression, MDACC grade, pTNM stage and lymph node metastasis significantly correlate to relapse in the Cox univariate analysis, in the multivariate Cox analysis only TK1 expression and lymph node metastasis were independent prognostic factors. The overall survival also correlated significantly to TK1 expression, MDACC grade, pTNM stage and lymph node metastasis in the Cox univariate analysis. However, only the pTNM stage was found to be an independent prognostic factor for survival in the Cox multivariate analysis. Therefore, though TK1 expression was an independent prognostic factor for relapse, but not for survival, TK1 is a more informative expression than Ki-67 for LI, relapse and overall survival rates. Thus, when TK1 is combined with MDACC grading, pTNM staging and lymph node metastasis, IHC determination of TK1 expression may improve the overall prediction of prognosis in patients with ovarian cancer.

A Chemiluminescent Protein Microarray Method for Determining the Seroglycoid Fucosylation Index.

The Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) is widely used to screen for hepatocellular carcinoma (HCC) in Japan and China. We developed a chemiluminescent protein microarray for determining the AFP-L3/AFP index (the ratio of AFP-L3 to total AFP, AFP-L3%) by fixing AFP-specific antibodies and Lens culinaris lectin on aldehyde-coated glass slides. Serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA) to validate the microarray. AFP-L3 was detected using Hotgen Biotech glycosyl capture spin column pretreatment technology and ELISA. When the AFP cut-off value was set to 20 ng/ml, the protein microarray displayed 89.74% sensitivity and 100% specificity for HCC diagnosis, and the ELISA displayed 87.17% sensitivity and 100% specificity. When the AFP-L3% cut-off value was set to 0.1, the protein microarray displayed 56.41% sensitivity and 100% specificity for HCC diagnosis, and the ELISA displayed 53.84% sensitivity and 100% specificity. The ROC curve for the HCC diagnosis showed that the AFP area under the ROC curve (AUC = 0.996; 95% CI: 0.986-1.005) was much higher than that of AFP-L3 (AUC = 0.857; 95% CI: 0.769-0.94) and AFP-L3% (AUC = 0.827; CI: 0.730-0.924). The microarray assay used in this study is a highly sensitive, accurate, and efficient assay for the determination of the AFP-L3%.

Serum TK1 is a more reliable marker than CEA and AFP for cancer screening in a study of 56,286 people.

BACKGROUND: The World Health Organization (WHO) has estimated that the number of cancer patients will increase by about 70% during the next 25 years world-wide. To deal with this problem, WHO has suggested a focus on prevention of tumor incidence and health screening for early detection of people with tumors. OBJECTIVE: To investigate the use of thymidine kinase 1 (TK1), CEA and AFP in serum to discover people with malignant tumors through health cancer screening. METHODS: Of a cohort in 486,085 people of a routine health screening at the Health Centre, Fujun 180 Hospital, Quanzhou city, China, 56,286 people were investigated according to the presence of cancer during 2009-2014. The concentration of CEA and AFP were determined by an electrochemiluminescence immunoassay from Roche Diagnostics e601GmbH and STK1 by a commercial kit based on an enhanced chemiluminescent dot blot assay. RESULTS: The cancer incident rate increased from 0.048/100,000 to 0.220/100,000. The most common types of tumors were those of the liver, cervix and lung. STK1 correlated to tumor growth rate, was more sensitive than CEA and AFP for discovering people with malignant tumors and more sensitive among people who had diagnosis of malignant tumor. STK1 was also a prognostic biomarker for death at 10-40 months follow-up, while CEA and AFP were not. A combination of these markers increased the sensitivity by about 30%. CONCLUSION: STK1 is a reliable biomarker for discovering people with malignant tumors in cancer screening.

Serum thymidine kinase 1 is a reliable maker for the assessment of the risk of developing malignancy: A case report.

With regard to different types of malignancies, thymidine kinase 1 (TK1) is a useful prognostic marker in clinical oncology, both as a serum proliferation marker and in immunohistochemistry. The present study investigated the use of serum TK1 protein (STK1p) for the identification of multiple proliferating diseases linked to the risk of developing cancer, by following one patient during the period of 2003-2014. The patient presented with adenomatous polyps in the stomach in 2003, follicular cervicitis in 2007 and hyperplasia of the breast/fibrocystic breasts in 2010. The breast cysts increased from 4×5 mm in size in 2010 to 8×7 mm in size in 2013, and were assessed as a suspicious malignancy at the end of this period. In parallel, the STK1p values increased from 2.0 to 7.6 pM. Based on this information, a minimally invasive surgery using the Mammotome® Biopsy System was performed. Immunohistochemistry on the cyst tissue showed strong staining of TK1 in the ductal epithelial cells and thus confirmed the abnormal proliferation in the lesion. One week after the surgery, the STK1p value had decreased to almost normal values (1.6 pM), but then fluctuated above 2.0 pM for the next 7 months. After the surgery, the patient was re-examined and small foci with squamous cell hyperplasia and a suspected ulcerated cervix, as well as flat gastric erosive, were identified, but not treated; this may explain why the STK1 P-values did not return to within normal values. The patient is currently being followed up using STK1p analysis combined with imaging/pathology in order to begin therapeutic intervention as early as possible to avoid the risk of developing cancer. Overall, STK1p is useful in health screening to identify individuals at risk of developing premalignancy/malignancy.

Thymidine kinase 1 is a better prognostic marker than Ki-67 for pT1 adenocarcinoma of the lung.

OBJECTIVES: The sensitivity and reliability of the biomarkers thymidine kinase 1 (TK1) and Ki-67 were studied in relation to clinical features and prognosis of survival for pathological-T1 (pT1) lung adenocarcinoma patients. METHODS: TK1 and Ki-67 expression was determined in 80 patients with pT1 adenocarcinoma of the lung and in 20 specimens from normal lung tissues, using immunohistochemistry. RESULTS: TK1 was found in most lung tumor cells both in the cytoplasm and the nuclei. The positive labelling index (LI) for total TK1 was significantly higher than that for Ki-67. There was a significant correlation between the LI of total TK1 and lymph node metastasis, degree of tumor invasion and pathologic stages, which was not found for Ki-67. In addition, the overall 5-year survival of patients was statistically significant different between low and high levels of TK1 expression, but not in cases of Ki-67. A multivariate analysis revealed that expression of TK1, lymph node involvement and TNM pathology staging could serve as independent prognostic factors for the disease progression of pT1 lung adenocarcinoma patients. CONCLUSIONS: Compared with Ki-67, TK1 is a more reliable proliferation index in pT1 adenocarcinoma of lung, which can evaluate the invasion and the prognosis of tumor.