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1.
Hematology ; 27(1): 778-784, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35793786

RESUMO

BACKGROUND/OBJECTIVE: Bone marrow biopsy, the gold standard for the diagnosis of multiple myeloma (MM), has main limitation of the invasiveness. Here, we explored the diagnostic and prognostic values of circulating miR-1246 in patients with MM. MATERIAL AND METHODS: Ninety MM patients and 30 healthy donors (control group) were recruited in this study. The expression of miR-1246 in the peripheral blood samples was detected using qPCR. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-1246 in MM. The Kaplan-Meier survival analyze was performed to evaluate the prognostic value of miR-1246. RESULTS: The expression level of serum miR-1246 from newly diagnosed MM patients was significantly higher than that of the control group. Circulating miR-1246 level was decreased after treatment in remission patients, but remained high levels in relapsed patients (P < 0.05). ROC analysis demonstrated that miR-1246 showed a high diagnostic value in MM with an area under the curve (AUC) of 0.952, the sensitivity of 87%, and the specificity of 95% [95% confidence interval (CI) 0.902-1.007; P < 0.001]. Kaplan-Meier analysis showed that the progression-free survival (PFS) (14.0 months vs. 26.5 months, P = 0.045) and overall survival (OS) (20.5 months vs. 55.5 months, P = 0.014) were significantly shorter in patients with high miR-1246 expression as compared with those in patients with miR-1246 low expression. Multiple Cox regression model analysis showed that circulating miR-1246 was an independent prognostic factor for PFS (HR 2.786, 95% CI: 1.420-5.467, P = 0.003) and OS (HR 2.995, 95% CI: 1.166-7.689, P = 0.023) in MM patients. CONCLUSION: This study demonstrates that circulating miR-1246 level is elevated in MM patients, which shows high values in the diagnosis and prognosis prediction in patients with MM.


Assuntos
MicroRNAs , Mieloma Múltiplo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/sangue , MicroRNAs/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico
2.
Dis Markers ; 2022: 7087885, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35818587

RESUMO

Purpose: The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods: Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results: mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion: Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.


Assuntos
Antígeno Carcinoembrionário , Neoplasias Colorretais , Septinas , Biomarcadores Tumorais/sangue , Antígeno CA-19-9 , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Septinas/sangue
3.
World J Surg Oncol ; 20(1): 225, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794603

RESUMO

BACKGROUND: The important role that the immune system plays in malignant diseases is well known. The action of interleukin-7 (IL-7) as a cytokine has been observed in many cellular processes, both in normal cells of the immune system and in some cancer cells. The aim of this study has been to explore whether there is any elevation of interleukin-7 serum levels in early invasive breast cancer (EIBC) patients in comparison with healthy controls. In addition, the correlation between the IL-7 serum level and the histopathological characteristics of the tumor has been evaluated. METHODS: This cross-sectional, observational, and analytical study included 213 consecutive patients with EIBC (113 from Croatia and 100 from Kosovo) and 62 healthy participants as the control group (30 from Croatia and 32 from Kosovo). Blood samples have been taken from patients confirmed with breast cancer (BC) by biopsy, prior to surgical intervention and other oncological treatments, as well as from healthy participants. A serum IL-7 level has been measured, using the "Sandwich" ELISA Immunoenzyme test. In addition, after the surgical intervention, histopathological specimen examinations and immunohistochemistry have been performed and analyzed. The differences in the distribution of the numerical variables have been analyzed with the Mann-Whitney U test and Kruskal-Wallis ANOVA test. Correlations have been tested with Pearson coefficients. A P-value < 0.05 has been accepted as statistically significant. RESULTS: The serum level of IL-7 in EIBC patients was significantly higher than in control cases (P 0.001). Patients with invasive lobular carcinoma (ILC) seem to have a lower IL-7 serum level compared to other histological subtypes, and the difference has been significant (P = 0.043). There has been no correlation between IL-7 serum level and histopathological characteristics of the tumor, with neither age nor menopausal status of the patients. CONCLUSIONS: Noting the significant increase in the IL-7 serum level in the EIBC patients as compared to the healthy control group, the use of IL-7 as a potential diagnostic indicator for BC, as well as in the follow-up of the patients after treatment, can be assumed. The lack of correlation with tumor size, lymph node metastasis, and all other histopathological characteristics of the tumor questions its use as a prognostic indicator.


Assuntos
Neoplasias da Mama , Interleucina-7 , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Interleucina-7/sangue , Prognóstico
4.
Mol Med ; 28(1): 67, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715741

RESUMO

BACKGROUND: Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression. METHODS: Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation, viability, migration assays, RNA-seq, and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells. RESULTS: Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression, whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy. CONCLUSIONS: Hypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Metilação de DNA , Proteínas de Membrana , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ilhas de CpG , Progressão da Doença , Feminino , Hormônios , Humanos , Proteínas de Membrana/biossíntese , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Valor Preditivo dos Testes
5.
Bull Exp Biol Med ; 173(2): 261-264, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35737160

RESUMO

We performed a comparative quantitative analysis of LINE-1 mRNA levels in extracellular total plasma RNA in patients with colon cancer and practically healthy donors. Quantitative multiplex PCR with reverse transcription was used to assess the level of LINE-1 and 18S rRNA mRNA in extracellular total plasma RNA. The median of LINE-1 mRNA values in colon cancer patients (4.95) was significantly higher than in healthy donors (2.3) (p=0.037). It was shown for the first time that the level of LINE-1 mRNA in total RNA from blood plasma can be determined in the format of a liquid biopsy and serve as a new potential non-invasive marker of colon cancer.


Assuntos
Ácidos Nucleicos Livres , Neoplasias do Colo , Neoplasias Colorretais , Proteínas de Ligação a RNA , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Neoplasias do Colo/sangue , Neoplasias do Colo/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , RNA Mensageiro/sangue , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
Bioengineered ; 13(6): 14204-14214, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35754345

RESUMO

Colorectal cancer (CRC) is a common gastrointestinal cancer with high incidence and mortality rates. CRC may be associated with regulation of circulating nucleotides. This study aimed to evaluate the serum levels of nucleotide-metabolizing enzymes (ATPase and AMPase) in patients with CRC and to explore the clinical diagnostic value of these enzymes. The gene set variation analysis (GSVA) score of the ATP-adenosine signature was calculated using tumor samples from The Cancer Genome Atlas (TCGA). ATP-adenosine signaling plays a central role in CRC progression. A total of 135 subjects, including 87 patients with CRC and 48 healthy controls, were included. The serum levels of ATPase and AMPase in the CRC group were significantly higher than those in the control group (P < 0.05). Furthermore, ATP and AMP hydrolysis levels significantly increased in the advanced CRC group (P < 0.05). ATP and AMP hydrolysis was decreased by the ENTPDase inhibitors (POM-1 and ARL67156) and CD73 inhibitor (APCP). The sensitivities of ATPase and AMPase were 95.4% and 75.9%, respectively, which were higher than those of CEA (67.8%) and CA19-9 (72.4%). The specificities of ATPase and AMPase were 69.9% and 73.9%, respectively, which were higher than that of CA19-9 (47.8%). The combination of CEA, ATPase, and AMPase demonstrated high sensitivity (92.0%) and specificity (87.0%). Collectively, ATPase and AMPase activities are upregulated in CRC with considerable diagnostic significance. The combination of CEA, ATPase, and AMPase may provide a novel approach for CRC screening.


Assuntos
Monofosfato de Adenosina , Adenosina Trifosfatases , Trifosfato de Adenosina , Neoplasias Colorretais , Nucleotidases , Monofosfato de Adenosina/sangue , Adenosina Trifosfatases/sangue , Adenosina Trifosfatases/genética , Trifosfato de Adenosina/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Humanos , Nucleotidases/sangue , Nucleotidases/genética
7.
Methods Mol Biol ; 2453: 101-117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35622323

RESUMO

Liquid biopsy is a novel diagnostic approach at first developed to characterize the molecular profile of solid tumors by analyzing body fluids. For cancer patients, it represents a noninvasive way to monitor the status of the solid tumor with respect to representative biomarkers. There is growing interest in the utilization of circulating tumor DNA (ctDNA) analysis also in the diagnostic and prognostic fields of lymphomas. Clonal immunoglobulin (IG) gene rearrangements are fingerprints of the respective lymphoid malignancy and thus are highly suited as specific molecular targets for minimal residual disease (MRD) detection. Tracing of the clonal IG rearrangement patterns in ctDNA pool during treatment can be used for MRD assessment in B-cell lymphomas. Here, we describe a reproducible next-generation sequencing assay to identify and characterize clonal IG gene rearrangements for MRD detection in cell-free DNA.


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Rearranjo Gênico , Genes de Imunoglobulinas , Linfoma , Neoplasia Residual , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Células Clonais , Rearranjo Gênico/genética , Genes de Imunoglobulinas/genética , Humanos , Imunoglobulinas/genética , Biópsia Líquida/métodos , Linfoma/sangue , Linfoma/diagnóstico , Linfoma/genética , Linfoma de Células B/sangue , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Neoplasia Residual/sangue , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética
8.
Anticancer Res ; 42(6): 3169-3176, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35641260

RESUMO

BACKGROUND/AIM: Increased serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9) are established prognostic factors in ampulla of Vater carcinoma (AC). We determined the best cut-off values of preoperative CEA and CA19-9 and compared the prognostic power of preoperative CEA with that of preoperative CA19-9 for overall survival (OS). PATIENTS AND METHODS: A total of 116 consecutive patients without jaundice who underwent macroscopic curative resection for AC between January 2002 and August 2019 were enrolled. RESULTS: Using the minimum p-value approach based on the OS, the optimal CEA cut-off value was found to be 6.5 ng/ml; however, the cut-off value of CA19-9 could not be determined, as no significant p value was identified. The OS of the patients with CEA >6.5 ng/ml (n=5; 3-year OS, 20.0%) was significantly worse than that with CEA ≤6.5 ng/ml (n=111; 3-year OS, 76.6%; p<0.001). A Cox proportional hazards analysis for OS revealed CEA >6.5 ng/ml (hazard ratio=4.01, p=0.019) to be an independent prognostic factor. CONCLUSION: In patients with AC, although the CA19-9 optimal cut-off value could not be determined, CEA >6.5 ng/ml independently affected long-term survival after resection.


Assuntos
Ampola Hepatopancreática , Antígeno CA-19-9 , Antígeno Carcinoembrionário , Carcinoma , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma/diagnóstico , Carcinoma/cirurgia , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida
9.
Clin Cancer Res ; 28(12): 2579-2586, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35561344

RESUMO

PURPOSE: We sought to determine whether the detection of circulating tumor DNA (ctDNA) in samples of patients undergoing chemotherapy for advanced leiomyosarcoma (LMS) is associated with objective response or survival. EXPERIMENTAL DESIGN: Using ultra-low-passage whole-genome sequencing (ULP-WGS) of plasma cell-free DNA from patients treated on a prospective clinical trial, we tested whether detection of ctDNA evaluated prior to the start of therapy and after two cycles of chemotherapy was associated with treatment response and outcome. Associations between detection of ctDNA and pathologic measures of disease burden were evaluated. RESULTS: We found that ctDNA was detectable by ULP-WGS in 49% patients prior to treatment and in 24.6% patients after two cycles of chemotherapy. Detection of pretreatment ctDNA was significantly associated with a lower overall survival [HR, 1.55; 95% confidence interval (CI), 1.03-2.31; P = 0.03] and a significantly lower likelihood of objective response [odds ratio (OR), 0.21; 95% CI, 0.06-0.59; P = 0.005]. After two cycles of chemotherapy, patients who continued to have detectable levels of ctDNA experienced a significantly worse overall survival (HR, 1.77; 95% CI, 1-3.14; P = 0.05) and were unlikely to experience an objective response (OR, 0.05; 95% CI, 0-0.39; P = 0.001). CONCLUSIONS: Our results demonstrate that detection of ctDNA is associated with outcome and objective response to chemotherapy in patients with advanced LMS. These results suggest that liquid biopsy assays could be used to inform treatment decisions by recognizing patients who are likely and unlikely to benefit from chemotherapy. See related commentary by Kasper and Wilky, p. 2480.


Assuntos
DNA Tumoral Circulante , Leiomiossarcoma , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/genética , Mutação , Estudos Prospectivos
10.
Clin Chim Acta ; 531: 318-324, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35500878

RESUMO

BACKGROUND: Early diagnosis is of great significance for the prognosis of colorectal cancer (CRC) patients. Either serum cystatin S (CST4) or DR-70 has been demonstrated to play an important role on the diagnosis for CRC, however, the diagnostic performances of individual and combined detection of serum CST4 and DR-70 for the patients with CRC at early stage have still not been clarified up to now. METHODS: The performances of CST4 and DR-70 were evaluated by ELISA for the early diagnosis of CRC with 288 retrospective serum samples. A training set comprised of 64 patients with early CRC, 64 patients with colorectal benign lesions (CBL), and 64 healthy controls (HC) was used to develop the predictive model for early CRC. And then, data obtained from an independent validation set was applied to evaluate and validate the predictive model. RESULTS: In the training set, the levels of CST4 and DR-70 in early CRC group were significantly higher than that in CBL group/HC group (P < 0.001); serum CST4 presented the AUC of 0.927 for early CRC patients, with 57.8% sensitivity at 95.3% specificity; serum DR-70 presented the AUC of 0.725 for early CRC patients, with 29.7% sensitivity at 95.3% specificity; combination of serum CST4 and DR-70 presented the AUC of 0.941, with 68.8% sensitivity at 93.8% specificity. Additionally, the combination of serum CST4 and DR-70 showed the AUC of 0.940 for early CRC patients, with 71.9 % sensitivity at 89.1% specificity in the validation set. CONCLUSIONS: Both serum CST4 and DR-70 present the diagnostic value for the patients with early CRC, and the combination of CST4 and DR-70 contributes to the further improvement of the early diagnosis for CRC.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Detecção Precoce de Câncer , Cistatinas Salivares , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Humanos , Prognóstico , Estudos Retrospectivos , Cistatinas Salivares/sangue
11.
Neurosurgery ; 91(2): 231-238, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35535984

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined. OBJECTIVE: To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA. METHODS: PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated. RESULTS: Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance ( P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies. CONCLUSION: ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.


Assuntos
DNA Tumoral Circulante , Glioma , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/líquido cefalorraquidiano , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/líquido cefalorraquidiano , DNA Tumoral Circulante/genética , Glioma/diagnóstico , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
12.
J Clin Lab Anal ; 36(6): e24411, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35446997

RESUMO

PURPOSE: To find a useful disease marker for early diagnosis of gastric cancer, we tried to explore the expression of serum miR-181, miR-652, and carbohydrate antigen 72-4 (CA72-4). PATIENTS AND METHODS: According to clinical pathologic stages, 112 patients with gastric cancer were divided into early gastric cancer group (n = 60) and advanced gastric cancer group (n = 52), stage I-II (n = 65), and stage III-IV (n = 47). Another 50 cases of gastric benign lesions and 40 healthy controls were also selected. Real-time quantitative PCR together with chemiluminescence were applied to detect expression levels. ROC curve was applied to judge their diagnostic efficiency. Pearson's correlation analysis was put into use to investigate the relevance of three indicators. RESULTS: Compared with benign lesions group and control group, significantly higher expression levels were found in patients of gastric cancer (all p < 0.001). Similarly, compared with early gastric cancer group, significantly higher expression levels were found in advanced gastric cancer group (all p < 0.001). The same result was also found in stage III-IV (all p < 0.001). The best cutoff values were 0.93, 2.38, and 16.94 U/ml, respectively. The area under the curve (0.917, 95%CI: 0.856-0.975) of the three combined diagnosis of early gastric cancer was the largest, and its sensitivity and specificity were 92.5% and 86.8%. And miR-181 and miR-652 were positively correlated with CA72-4 (r = 0.772, p < 0.001, r = 0.853, p < 0.001). CONCLUSION: Serum miR-181, miR-652, and CA72-4 are closely linked to the occurrence and development of gastric cancer. Combination of three indicators has diagnostic value for early gastric cancer.


Assuntos
Antígenos Glicosídicos Associados a Tumores , Detecção Precoce de Câncer , MicroRNAs , Neoplasias Gástricas , Antígenos Glicosídicos Associados a Tumores/biossíntese , Antígenos Glicosídicos Associados a Tumores/sangue , Antígenos Glicosídicos Associados a Tumores/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Humanos , MicroRNAs/biossíntese , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico , Curva ROC , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
13.
J Cancer Res Ther ; 18(1): 152-157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35381777

RESUMO

Background: Cervical cancer is one of the common cancers in females. The common method of screening is Pap test which has low sensitivity. Hence, better methods are explored with different biomarkers, of which estimation of P16 protein can be opted in early detection of cervical cancer. Materials and Methods: Seventy cases and seventy controls were considered for the study. Cases were invasive squamous cell carcinoma (SCC) of cervix confirmed by histopathology. Controls were healthy age-matched females. The blood sample of cases and controls was collected in K2 Ethylenediaminetetraacetic acid vacutainer, and the separated plasma was subjected to estimation of P16 protein by quantitative sandwich Enzyme-Linked ImmunoSorbent Assay method. The data were analyzed for the association between p16 protein in plasma in cases and controls. Results: The age among cases and controls ranged from 30 to 80 years. The P16 levels among cases ranged from 3.4 to 19.6 ng/ml with a mean of 7.24 ± 2.35 ng/ml. The plasma P16 level in controls ranged between 0.9 and 9.7 ng/ml with mean of 4.1 ± 2.22 ng/ml. At cutoff more than 4.8 ng/ml in cases, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.86%, 72.86%, 77.4%, 91.1%, and 82.86%, respectively. The specificity increased with increase in plasma p16 levels. The P16 levels were maximum in stage IV disease. Conclusion: This was a pilot study to detect the plasma p16INK4a levels in SCC of cervix. The levels of plasma p16 protein between 3.9 and 5 ng/ml can be considered as the range for the test to be positive. In clinically suspected cases of cervical cancer, levels more than 4.8 ng/ml can be considered for the diagnosis as point of care test.


Assuntos
Carcinoma de Células Escamosas , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias do Colo do Útero , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Colo do Útero/patologia , Inibidor p16 de Quinase Dependente de Ciclina/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias do Colo do Útero/patologia
14.
Neoplasma ; 69(3): 729-740, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35471981

RESUMO

The value of serum tumor biomarkers used for lung cancer diagnosis is still controversial in clinical practice. This study aimed to further dissect and evaluate the clinical value of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1) together with a potential new biomarker, the human epididymis protein 4 (HE4) for lung cancer diagnosis, in a large cohort of a Chinese population. Ostensibly healthy individuals, as well as those with benign non-cancerous diseases, benign tumors, lung cancers, and other types of malignancies, were enrolled in the study. Serum ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were analyzed using the chemiluminescence immunoassay. Data were analyzed utilizing the SPSS and GraphPad Prism software. Detailed dissection of the diagnostic characteristics of serum 6 biomarkers on lung cancer was performed. All 6 biomarkers showed capabilities in characterizing lung cancer from other diseases. ProGRP and NSE were highly specific to small cell lung cancer (SCLC); SCC-Ag was a fair biomarker for NSCLC, specifically SCC histotype; CEA showed specificity to SCLC, followed by NSCLC; CYFRA21-1 was a good biomarker for both SCLC and NSCLC; HE4 showed high specificity to SCLC. For NSCLC characterization, CYFRA21-1+HE4+CEA was the best combinatory pattern in the terms of diagnostic performance (AUC=0.8110). The best combinatory analysis for SCLC was ProGRP+NSE+HE4 (AUC=0.9282). Patients with advanced stage, larger tumor, males, and age 50 or older had higher serum biomarkers levels than those with early stage, smaller tumor, females, and age under 50. Six biomarkers had capabilities in characterizing lung cancer with high or fair diagnostic performance. HE4 is a potential biomarker for both SCLC and NSCLC diagnosis, which merits further investigation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Humanos , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo
15.
Dis Markers ; 2022: 3424413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251370

RESUMO

BACKGROUND: Reports on the expression of CD38 in Sézary syndrome (SS), erythrodermic primary cutaneous T cell lymphoma with leukemic involvement, are limited. The aim of the present study is the analysis of the expression of CD38 by skin-infiltrating mononuclear cells and circulating T lymphocytes in a cohort of SS patients. METHODS: SS patients diagnosed since 1985 in our clinic were retrospectively analyzed for CD38 expression in biopsy and blood samples by immunohistochemistry and flow cytometry, respectively. RESULTS: SS patients show a predominant CD38-negative phenotype on both skin and blood. A subgroup of patients was found expressing CD38 (12 cases) in either the skin (>25% cell infiltrate) or blood (CD4+CD38+ >50%), among whom 4 in the blood, 7 in the skin, and 1 in both blood and skin. CONCLUSION: The implications of these observations may be twofold: the relevance in basic science is related to a potential role in immune defense regulation, whilst in perspective CD38 may become a target for antibody therapy, considering the availability of different anti-CD38 monoclonal antibodies.


Assuntos
ADP-Ribosil Ciclase 1/imunologia , Biomarcadores Tumorais/sangue , Citometria de Fluxo , Imuno-Histoquímica , Glicoproteínas de Membrana/imunologia , Síndrome de Sézary , Neoplasias Cutâneas , ADP-Ribosil Ciclase 1/genética , Biópsia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/ultraestrutura , Feminino , Humanos , Contagem de Linfócitos , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sézary/imunologia , Síndrome de Sézary/patologia , Pele/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/ultraestrutura
16.
Dis Markers ; 2022: 6657820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273656

RESUMO

Purpose: This study is aimed at evaluating serum autoantibodies against four tumor-associated antigens, including LRDD, STC1, FOXA1, and EDNRB, as biomarkers in the immunodiagnosis of ovarian cancer (OC). Methods: The autoantibodies against LRDD, STC1, FOXA1, and EDNRB were measured using an enzyme-linked immunosorbent assay (ELISA) in 94 OC patients and 94 normal healthy controls (NHC) in the research group. In addition, the diagnostic values of different autoantibodies were validated in another independent validation group, which comprised 136 OC patients, 136 NHC, and 181 patients with benign ovarian diseases (BOD). Results: In the research group, autoantibodies against LRDD, STC1, and FOXA1 had higher serum titer in OC patients than NHC (P < 0.001). The area under receiver operating characteristic curves (AUCs) of these three autoantibodies were 0.910, 0.879, and 0.817, respectively. In the validation group, they showed AUCs of 0.759, 0.762, and 0.817 and sensitivities of 49.3%, 42.7%, and 48.5%, respectively, at specificity over 90% for discriminating OC patients from NHC. For discriminating OC patients from BOD, they showed AUCs of 0.718, 0.729, and 0.814 and sensitivities of 47.1%, 39.0%, and 51.5%, respectively, at specificity over 90%. The parallel analyses demonstrated that the combination of anti-LRDD and anti-FOXA1 autoantibodies achieved the optimal diagnostic performance with the sensitivity of 58.1% at 87.5% specificity and accuracy of 72.8%. The positive rate of the optimal autoantibody panel improved from 62.4% to 87.1% when combined with CA125 in detecting OC patients. Conclusion: Serum autoantibodies against LRDD, STC1, and FOXA1 have potential diagnostic values in detecting OC.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/imunologia , Fator 3-alfa Nuclear de Hepatócito/imunologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Receptores de Superfície Celular/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Estudos Retrospectivos , Adulto Jovem
17.
BMC Cancer ; 22(1): 221, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227234

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablation using radiofrequency ablation (RFA) or microwave ablation (MWA) is potentially curative for early-stage HCC with outcomes comparable to surgical resection. We explored the influence of demographic, clinical, and laboratory factors on outcomes of HCC patients receiving ablation. METHODS: This retrospective cohort study included 221 HCC patients receiving local ablation at Mayo Clinic between January 2000 and October 2018, comprising 140 RFA and 81 MWA. Prognostic factors determining overall survival (OS) and disease-free survival (DFS) were identified using multivariate analysis. RESULTS: There was no clinically significant difference in OS or DFS between RFA and MWA. In multivariate analysis of OS, pre-ablation lymphocyte-monocyte ratio [Hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.58-0.84, P = 0.0001], MELD score [HR 1.12, 95%CI 1.068-1.17, P <  0.0001], tumor number [HR 1.23, 95%CI 1.041-1.46, P = 0.015] and tumor size [HR 1.18, 95%CI 1.015-1.37, P = 0.031] were clinically-significant prognostic factors. Among HCC patients with chronic hepatitis C (HCV) infection, positive HCV PCR at HCC diagnosis was associated with 1.4-fold higher hazard of death, with 5-year survival of 32.8% vs 53.6% in HCV PCR-negative patients. Regarding DFS, pre-ablation lymphocyte-monocyte ratio [HR 0.77, 95%CI 0.66-0.9, P = 0.001], MELD score [HR 1.06, 95%CI 1.022-1.11, P = 0.002], Log2 AFP [HR 1.11, 95%CI 1.033-1.2, P = 0.005], tumor number [HR 1.29, 95%CI 1.078-1.53, P = 0.005] and tumor size [HR 1.25, 95%CI 1.043-1.51 P = 0.016] were independently prognostic. CONCLUSIONS: Pre-ablation systemic inflammation represented by lymphocyte-monocyte ratio is significantly associated with OS and DFS in HCC patients treated with local ablation. HCV viremia is associated with poor OS. Tumor biology represented by tumor number and size are strongly prognostic for OS and DFS while AFP is significantly associated with DFS only.


Assuntos
Carcinoma Hepatocelular/sangue , Hepatite C Crônica/sangue , Mediadores da Inflamação/sangue , Neoplasias Hepáticas/sangue , Ablação por Radiofrequência , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Dis Markers ; 2022: 7758735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308139

RESUMO

Objectives: To discover a more powerful diagnostic tool for the detection of hepatocellular carcinoma (HCC). Methods: 16 extracellularly located candidates were selected by analyzing the expression array datasets in GEO. 10 of them were validated in clinical samples by ELISA. Differences of each variable were compared by one-way ANOVA or Kruskal-Wallis test. CCL20 and LCN2 were determined in all samples (HCC, 167; liver cirrhosis, 106; and healthy control, 106) and finally chosen for the construction of the combination model by binary logistic regression. The models were first built using a comprehensive control, including both liver cirrhosis (LC) and healthy donors. Then, the models were rebuilt by using the LC group alone as a control. ROC analysis was performed to compare the diagnostic efficiency of each indicator. Results: Levels of CCL20 and LCN2 in HCC sera were significantly higher than those in all controls. Using the comprehensive control, ROC curves showed that the optimum diagnostic cutoff of the CCL20 and LCN2 combination was 0.443 (area under curve (AUC) of 0.927 (95% CI 0.896-0.951), sensitivity of 0.808, specificity of 0.892, and accuracy of 0.859). For detection of HCC from LC control, the optimum diagnostic cutoff was 0.590 (AUC of 0.919 (95% CI 0.880-0.948), sensitivity of 0.814, specificity of 0.868, and accuracy of 0.834). Furthermore, the model maintained diagnostic accuracy for patients with HCC in the early stage, with the sensitivity and specificity of 0.75 and 0.77 from LC control, yet the AFP only reached 0.5 and 0.67, respectively. Conclusion: A combination model composed of CCL20 and LCN2 may serve as a more efficient tool for distinguishing HCC from nonmalignant liver diseases.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Quimiocina CCL20/sangue , Lipocalina-2/sangue , Neoplasias Hepáticas/diagnóstico , Bases de Dados Genéticas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Transcriptoma
20.
Comput Math Methods Med ; 2022: 8979404, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281945

RESUMO

The objective of this study was to analyze the value of artificial intelligence algorithm-based computerized tomography (CT) image combined with serum tumor markers for diagnoses of pancreatic cancer. In the study, 68 hospitalized patients with pancreatic cancer were selected as the experimental group, and 68 hospitalized patients with chronic pancreatitis were selected as the control group, all underwent CT imaging. An image segmentation algorithm on account of two-dimensional (2D)-three-dimensional (3D) convolution neural network (CNN) was proposed. It also introduced full convolutional network (FCN) and UNet network algorithm. The diagnostic performance of CT, serum carbohydrate antigen-50 (CA-50), serum carbohydrate antigen-199 (CA-199), serum carbohydrate antigen-242 (CA-242), combined detection of tumor markers, and CT-combined tumor marker testing (CT-STUM) for pancreatic cancer were compared and analyzed. The results showed that the average Dice coefficient of 2D-3D training was 84.27%, which was higher than that of 2D and 3D CNNs. During the test, the maximum and average Dice coefficient of the 2D-3D CNN algorithm was 90.75% and 84.32%, respectively, which were higher than the other two algorithms, and the differences were statistically significant (P < 0.05). The penetration ratio of pancreatic duct in the experimental group was lower than that in the control group, the rest were higher than that in the control group, and the differences were statistically significant (P < 0.05). CA-50, CA-199, and CA-242 in the experimental group were 141.72 U/mL, 1548.24 U/mL, and 83.65 U/mL, respectively, which were higher than those in the control group, and the differences were statistically significant (P < 0.05). The sensitivity, specificity, positive predictive value, and authenticity of combined detection of serum tumor markers were higher than those of CA-50, CA-199, and CA-242, and the differences were statistically significant (P < 0.05). The results showed that the proposed algorithm 2D-3D CNN had good stability and image segmentation performance. CT-STUM had high sensitivity and specificity in diagnoses of pancreatic cancer.


Assuntos
Algoritmos , Biomarcadores Tumorais/sangue , Tomografia Computadorizada Multidetectores/estatística & dados numéricos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Inteligência Artificial , Estudos de Casos e Controles , Biologia Computacional , Feminino , Humanos , Imageamento Tridimensional/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Pancreatite Crônica/sangue , Pancreatite Crônica/diagnóstico por imagem , Sensibilidade e Especificidade
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