Evolutionary insights into sequence modifications governing chitin recognition and chitinase inactivity in YKL-40 (HC-gp39, CHI3L1).

YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity. Contrary to the common belief associating the lack of chitinase activity with amino acid substitutions in the catalytic motif, attempts to activate YKL-40 by creating two amino acid mutations in the catalytic motif (MT-YKL-40) proved ineffective. Subsequent exploration that included creating chimeras of MT-YKL-40 and CHIT1 catalytic domains (CatDs) identified key exons responsible for YKL-40 inactivation. Introducing YKL-40 exons 3, 6, or 8 into CHIT1 CatD resulted in chitinase inactivation. Conversely, incorporating CHIT1 exons 3, 6, and 8 into MT-YKL-40 led to its activation. Our recombinant proteins exhibited properly formed disulfide bonds, affirming a defined structure in active molecules. Biochemical and evolutionary analysis indicated that the reduced chitinase activity of MT-YKL-40 correlates with specific amino acids in exon 3. M61I and T69W substitutions in CHIT1 CatD diminished chitinase activity and increased chitin binding. Conversely, substituting I61 with M and W69 with T in MT-YKL-40 triggered chitinase activity while reducing the chitin-binding activity. Thus, W69 plays a crucial role in a unique subsite within YKL-40. These findings emphasize that YKL-40, though retaining the structural framework of a mammalian chitinase, has evolved to recognize chitin while surrendering chitinase activity.

The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients.

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

Primary Cilia as a Tumor Marker in Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis. Molecular findings demonstrated that 123 ciliary-associated genes (eg, doublecortin domain containing protein 2, Sintaxin-3, and centriolar coiled-coil protein 110) were dysregulated in PitNETs, representing the upregulation of markers at different stages of intracellular ciliogenesis. Our results demonstrate, for the first time, that ciliogenesis is increased in PitNETs, suggesting that this process might be used as a potential target for therapy in the future.

Using a CA19-9 Tumor Marker Gene Test to Assess Outcome After Pancreatic Cancer Surgery.

BACKGROUND: Cancer antigen 19-9 (CA19-9) is widely used as a marker of pancreatic cancer tumor burden and response to therapy. Synthesis of CA19-9 and its circulating levels are determined by variants encoding the fucosyltransferases, FUT2 and FUT3. Individuals can be grouped into one of four functional FUT groups (FUT3-null, FUT-low, FUT-intermediate, FUT-high), each with its own CA19-9 reference range based on its predicted capacity to produce CA19-9. The authors hypothesized that a FUT variant-based CA19-9 tumor marker gene test could improve the prognostic performance of CA19-9. METHODS: Preoperative and pre-treatment CA19-9 levels were measured, and FUT variants were determined in 449 patients who underwent surgery for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2010 and 2020, including 270 patients who underwent neoadjuvant therapy. Factors associated with recurrence-free and overall survival were determined in Cox proportional hazards models. RESULTS: Higher preoperative CA19-9 levels were associated with recurrence and mortality for patients in the higher-FUT groups (FUT-intermediate, FUT-high for mortality, with adjustment for other prognostic factors; hazard ratio [HR], 1.34 and 1.58, respectively; P < 0.001), but not for those in the lower-FUT groups (FUT3-null, FUT-low). As a tumor marker, CA19-9 levels of 100 U/ml or lower after neoadjuvant therapy and normalization of CA19-9 based on FUT group were more sensitive but less specific predictors of evidence for a major pathologic response to therapy (little/no residual tumor) and of early recurrence (within 6 months). CONCLUSION: Among patients undergoing pancreatic cancer resection, a CA19-9 tumor marker gene test modestly improved the prognostic performance of CA19-9.

Circulating tumor DNA (ctDNA) as a biomarker for lung cancer: Early detection, monitoring and therapy prediction.

Circulating tumor DNA (ctDNA), i.e., DNA shed from tumor cells into the bloodstream, is emerging as one of the most useful plasma biomarkers in patients with multiple types of cancer, including patients with non-small cell lung cancer (NSCLC). Indeed, NSCLC was the first malignancy in which measurement of ctDNA was approved for clinical use, i.e., mutational testing of EGFR for predicting response to EGFR tyrosine kinase inhibitors in patients with advanced disease. Although historically the gold standard method for EGFR mutational analysis required tumor tissue, the use of ctDNA is more convenient and safer for patients, results in a faster turn-around-time for return of results, provides a more complete representation of genetic alteration in heterogeneous tumors and is less costly to perform. Emerging uses of ctDNA in patients with lung or suspected lung cancer include screening for early disease, surveillance following initial treatment and monitoring response to therapy in metastatic disease. For evaluating therapy response, ctDNA appears to be especially useful in patients receiving targeted therapies against driver oncogenes or immunotherapy. Further work should not only validate these emerging findings but also aim to optimize and standardize ctDNA assays.

Pre-analytical stability of the CEA, CYFRA 21.1, NSE, CA125 and HE4 tumor markers.

BACKGROUND: For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols. OBJECTIVE: This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.1, HE4 and NSE for the following pre-analytical variables and procedures; i) whole blood stability, ii) serum freeze-thaw cycles, iii) electric vibration mixing and iv) serum storage at different temperatures. METHODS: Left-over patient samples were used and for every investigated variable six patient samples were used and analysed in duplicate. Acceptance criteria were based on analytical performance specifications based on biological variation and significant differences with baseline. RESULTS: Whole blood was stable for at least 6 hours for all TM except for NSE. Two freeze-thaw cycles were acceptable for all TM except CYFRA 21.1. Electric vibration mixing was allowed for all TM except for CYFRA 21.1. Serum stability at 4°C was 7 days for CEA, CA125, CYFRA 21.1 and HE4 and 4 hours for NSE. CONCLUSIONS: Critical pre-analytical processing step conditions were identified that, if not taken into account, will result in reporting of erroneous TM results.

Clinical Significance of the Post/Preoperative Anti-p53 Antibody Ratio in Predicting the Prognosis of Patients with Colorectal Cancer after Curative Surgery and Its Usefulness in Combination with Carcinoembryonic Antigen.

INTRODUCTION: Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. METHODS: In total, 1,223 patients with stage I-III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within 1 month preoperatively and 3 months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. RESULTS: Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. CONCLUSION: In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups.

Clinical application of serum tumor abnormal protein in prostate cancer patients.

PURPOSE: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. METHODS: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. RESULTS: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. CONCLUSION: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Impact of dynamic changes of tumor marker in neoadjuvant chemotherapy-treated triple-negative gastric cancer patients: a multi-center study.

BACKGROUND: Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199 < 37U/ml, CEA < 5 µg/ml and CA125 < 35U/ml) before and after neoadjuvant chemotherapy (NACT) remain unclear. METHODS: A total of 352 LAGC patients treated with NACT(NLAGC) from two centers were included. Of the 156 were Triple-negative patients. CA72-4 trajectory groupings was defined as longitudinal changes in CA72-4 levels before and after NACT to identify different potential subgroups and to compare recurrence-free survival (RFS) and overall survival (OS) among subgroups. The predictive performance of the nomogram-trajectory was evaluated using the area under the receiver operating characteristic curve(AUC), decision curve analysis, and C-index. RESULTS: In the Triple-negative patients, the Stable group had significantly worse 3-year OS than the Normal, Elevated, and Descend groups(3-year OS: 53.9% vs. 77.9% vs. 73.5% vs. 87.7%;P = 0.002). Cox multivariate analysis showed that CA72-4 trajectory groupings (Stable group: HR:3.442, 95%CI[1.574-7.528], P = 0.002) was an independent prognostic risk factor. In addition, the C-index and AUC values based on the nomogram-trajectory were significantly higher than those of ypTNM staging (C-index: 0.788 vs. 0.719,P < 0.001;AUC: 0.800 vs. 0.667,P < 0.001). Furthermore, The survival analysis revealed that the 3-year OS of the Low-Risk group of nomogram scores was significantly better than that of the High-Risk group(3-year OS:84.7% vs. 29.1%). And the Low-Risk group had the lower cumulative risk of recurrence (P < 0.001). CONCLUSION: The CA72-4 trajectory groupings were an independent prognostic factor for NLAGC Triple-negative patients. The predictive efficacy of the Nomogram-trajectory was significantly better than the ypTNM.

A preliminary study on the reference intervals of serum tumor marker in apparently healthy elderly population in southwestern China using real-world data.

BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. CONCLUSION: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.

OBJECTIVES: To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. METHODS: This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. RESULTS: We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79). CONCLUSION: Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

The platelet-to-lymphocyte ratio is a complementary prognostic factor to tumor markers in predicting early recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND: The usefulness of inflammation-based prognostic scores for early recurrence (ER) after hepatectomy for hepatocellular carcinoma has rarely been reported. This study aimed to evaluate the potential of inflammation-based prognostic scores as predictors of ER and their relationship with tumor markers. METHODS: We enrolled 338 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2021. Clinicopathological factors were compared between patients who developed ER (ER group) and those who did not develop ER (non-ER group). The association between inflammation-based prognostic scores and ER status was evaluated. These scores were compared with those of well-established tumor markers. RESULTS: The platelet-to-lymphocyte ratio (PLR) correlated with ER of hepatocellular carcinoma, with an area under the curve (AUC) value of 0.70, sensitivity of 68.1%, and specificity of 67.7%. In patients with low tumor marker levels, the PLR showed a strong correlation with ER of hepatocellular carcinoma, with an AUC value of 0.851, sensitivity of 100%, and specificity of 76.2%. Multivariate analysis revealed that the PLR was an independent prognostic factor for ER. CONCLUSIONS: The PLR is useful and complementary to tumor markers for predicting ER after hepatectomy for hepatocellular carcinoma.

Tumor markers determination in malignant pleural effusion: pearls and pitfalls.

Serum and pleural fluid tumor markers are well-recognized auxiliary diagnostic tools for malignant pleural effusion (MPE). Here, we discuss some pearls and pitfalls regarding the role of tumor markers in MPE management. The following issues are discussed in this article: What is the appropriate clinical scenario for evaluating pleural tumor markers? Which tumor markers should be advocated for diagnosing MPE? Can extremely high levels of tumor markers be employed to establish a diagnosis of MPE? Does the serum-to-pleural fluid ratio of a tumor marker have the same diagnostic efficacy as the measurement of that marker alone in the pleural fluid? Can tumor markers be used to estimate the risk of specific cancers? What should be considered when interpreting the diagnostic accuracy of tumor markers? How should tumor marker studies be performed? We addressed these issues with published works, particularly systematic reviews and meta-analyses.

External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA.

OBJECTIVES: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples. METHODS: CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020-2021) and KEQAS (2020-2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%). RESULTS: Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from -29.28 to 9.86 %, into -0.09-0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from -23.78 to 2.00 % pre-harmonization to -3.13-1.42 % post-harmonization. CONCLUSIONS: The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

Significance of changes in tumor markers in patients treated with durvalumab plus tremelimumab combination therapy as a surrogate marker for tumor response to unresectable hepatocellular carcinoma.

AIM: When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response. METHODS: Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur + Tre) were enrolled. Their functional reserve was Child-Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8 weeks after the start of treatment. The first radiological evaluation was carried out at 4 weeks and the second evaluation at 8-12 weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors. RESULTS: In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8 weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4 weeks. The optimal cut-off value to divide responders and nonresponders at 4 weeks was approximately -40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4 weeks. CONCLUSIONS: The change in tumor markers is a more useful predicter of tumor response to Dur + Tre than imaging evaluation alone.

A predictive nomogram developed and validated for gastric cancer patients with triple-negative tumor markers.

Aim: To predict the prognosis of gastric cancer patients with triple-negative tumor markers. Materials & methods: Prognostic factors of the nomogram were identified through univariate and multivariate Cox regression analyses. Calibration and receiver operating characteristic curves were used to assess accuracy. Decision curve analysis and concordance indexes were utilized to compare the nomogram with the pathological tumor, node, metastasis stage. Results: A nomogram incorporating log odds of positive lymph nodes, tumor size and lymphocyte-to-monocyte ratio was constructed. The calibration and receiver operating characteristic curves (area under the curve >0.85) showed high accuracy in predicting overall survival. The concordance indexes (0.832 vs 0.760; p < 0.001) and decision curve analysis demonstrated that the nomogram was superior to the pathological tumor, node, metastasis stage. Conclusion: A prediction and risk stratification nomogram has been developed and validated for gastric cancer patients with triple-negative tumor markers.

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 - 9 in the patients with diabetes.

OBJECTIVES: In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 - 9 (CA 19 - 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 - 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 - 9 in hospitalized patients with diabetes was the focus of our research. METHOD: A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. RESULTS: We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039. CONCLUSION: The percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. STRENGTHS AND LIMITATIONS OF THE STUDY: We studied the rate of hospitalized diabetic patients with elevated CA 19 - 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 - 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.

Establishment of tumor marker reference intervals for different age and gender groups in the healthy population of South China.

To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People's Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders.

The clinical characteristics of non-cystic fibrosis bronchiectasis patients with positive serum tumor markers: a retrospective study.

BACKGROUND: Serum tumor markers (STM), extensively used for the diagnosis, monitoring and prognostic assessment of tumors, can be increased in some non-malignant lung diseases. To date, there is a paucity of studies regarding the clinical characteristics of non-cystic fibrosis bronchiectasis patients with positive STMs. OBJECTIVE: To investigate the clinical characteristics and indicators of bronchiectasis with positive STMs. METHODS: The clinical data of 377 bronchiectasis patients was retrospectively collected from January 2017 to December 2019 from Beijing Chaoyang Hospital. Patients were divided into the STM negative group, the single STM positive group and the ≥2 STMs positive group according to the number of the positive STMs. The clinical characteristics are described and compared separately. The multivariate logistic regression analysis model was used to investigate the indicators regarding positive STMs. RESULTS: Patients in the ≥2 STMs positive group were older (P = 0.015), had higher mMRC scores (P < 0.001) and developed higher fever (P = 0.027). Additionally, these patients also had lower Albumin/Globulin Ratio (A/G), albumin (ALB), prealbumin (PAB) (P < 0.001, P < 0.001, P < 0.001, respectively) and higher CRP, ESR and Fbg (P < 0.001, P < 0.001 and P < 0.001, respectively). Age (OR 1.022, 95%CI 1.003-1.042; P = 0.026) and the number of affected lobes (OR 1.443, 95%CI 1.233-1.690; P < 0.001) were independently associated with one and ≥ 2 positive STMs in bronchiectasis patients. CONCLUSION: The ≥2 positive STMs are associated with a higher inflammation status and severer radiologic manifestations in bronchiectasis patients.

SERS biosensors based on catalytic hairpin self-assembly and hybridization chain reaction cascade signal amplification strategies for ultrasensitive microRNA-21 detection.

A highly sensitive surface-enhanced Raman scattering (SERS) biosensor has been developed for the detection of microRNA-21 (miR-21) using an isothermal enzyme-free cascade amplification method involving catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). The CHA reaction is triggered by the target miR-21, which causes hairpin DNA (C1 and C2) to self-assemble into CHA products. After AgNPs@Capture captures the resulting CHA product, the HCR reaction is started, forming long-stranded DNA on the surface of AgNPs. A strong SERS signal is generated due to the presence of a large amount of the Raman reporter methylene blue (MB) in the vicinity of the SERS "hot spot" on the surface of AgNPs. The monitoring of the SERS signal changes of MB allows for the highly sensitive and specific detection of miR-21. In optimal conditions, the biosensor exhibits a satisfactory linear range and a low detection limit for miR-21 of 42.3 fM. Additionally, this SERS biosensor shows outstanding selectivity and reproducibility. The application of this methodology to clinical blood samples allows for the differentiation of cancer patients from healthy controls. As a result, the CHA-HCR amplification strategy used in this SERS biosensor could be a useful tool for miRNA detection and early cancer screening.