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1.
Cancer Cell Int ; 21(1): 472, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493282

RESUMEN

BACKGROUND: CD9 is implicated in cancer progression and metastasis by its role in suppressing cancer cell proliferation and survival. However, the prognostic and clinicopathological significance of CD9 expression is controversial. Therefore, the current meta-analysis was conducted to determine the prognostic and clinicopathological significance of CD9 expression in cancer patients. METHODS: Eligible studies were selected through database search of PubMed, Embase and Cochrane library up to April 5 2020. The necessary data were extracted from the included studies. Pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the prognostic and clinicopathological significance of CD9 expression in cancer patients. RESULTS: A total of 17 studies consisting of 3456 cancer patients were included in this meta-analysis. An increased CD9 expression was significantly associated with a more favorable overall survival (OS) (HR 0.47, 95% CI 0.31-0.73, p = 0.001) and disease-free survival (DFS) (HR 0.48, 95% CI 0.30-0.79, p = 0.003). In subgroup analysis of cancer type, an increased CD9 expression was associated with increased OS in breast cancer and digestive system cancer, and with increased DFS in head and neck cancer and leukemia/lymphoma. Additionally, an increased CD9 expression significantly correlated with lower overall stage (OR 0.45, 95% CI 0.29-0.72, p = 0.001). CONCLUSION: An increased CD9 expression was associated with favorable survival in cancer patients suggesting that CD9 expression could be a valuable survival factor in cancer patients.

2.
Methods ; 179: 3-13, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32442672

RESUMEN

Digitizing whole-slide imaging in digital pathology has led to the advancement of computer-aided tissue examination using machine learning techniques, especially convolutional neural networks. A number of convolutional neural network-based methodologies have been proposed to accurately analyze histopathological images for cancer detection, risk prediction, and cancer subtype classification. Most existing methods have conducted patch-based examinations, due to the extremely large size of histopathological images. However, patches of a small window often do not contain sufficient information or patterns for the tasks of interest. It corresponds that pathologists also examine tissues at various magnification levels, while checking complex morphological patterns in a microscope. We propose a novel multi-task based deep learning model for HIstoPatholOgy (named Deep-Hipo) that takes multi-scale patches simultaneously for accurate histopathological image analysis. Deep-Hipo extracts two patches of the same size in both high and low magnification levels, and captures complex morphological patterns in both large and small receptive fields of a whole-slide image. Deep-Hipo has outperformed the current state-of-the-art deep learning methods. We assessed the proposed method in various types of whole-slide images of the stomach: well-differentiated, moderately-differentiated, and poorly-differentiated adenocarcinoma; poorly cohesive carcinoma, including signet-ring cell features; and normal gastric mucosa. The optimally trained model was also applied to histopathological images of The Cancer Genome Atlas (TCGA), Stomach Adenocarcinoma (TCGA-STAD) and TCGA Colon Adenocarcinoma (TCGA-COAD), which show similar pathological patterns with gastric carcinoma, and the experimental results were clinically verified by a pathologist. The source code of Deep-Hipo is publicly available athttp://dataxlab.org/deep-hipo.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Patología Clínica/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/patología , Mucosa Gástrica/patología , Humanos , Mucosa Intestinal/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología
3.
J Korean Med Sci ; 36(8): e56, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33650335

RESUMEN

BACKGROUND: Osteocalcin is known to regulate energy metabolism. Recently, metabolic syndrome (MetS) has been found to be associated with reduced levels of osteocalcin in men, as well as in postmenopausal women. The aim of this study was to investigate the association between serum osteocalcin and MetS in premenopausal women, compared with that in postmenopausal women. METHODS: This cross-sectional study was based on 5,896 participants who completed a health screening examination. They were classified according to their menopausal status. Each group was subdivided into non-MetS and MetS groups according to the modified National Cholesterol Education Program-Adult Treatment Panel III criteria. Serum osteocalcin levels were measured using the electrochemiluminescence immunoassay. RESULTS: Serum osteocalcin level was significantly lower in women with MetS than in those without MetS, after adjusting for confounders (14.12 ± 0.04 vs. 13.17 ± 0.13 [P = 0.004] in premenopausal women, and 20.34 ± 0.09 vs. 19.62 ± 0.21 [P < 0.001] in postmenopausal women), regardless of their menopausal status. Serum osteocalcin levels decreased correspondingly with an increasing number of MetS elements (P for trend < 0.001). Multiple regression analysis demonstrated that waist circumference (ß = -0.085 [P < 0.001] and ß = -0.137 [P < 0.001]) and hemoglobin A1c (ß = -0.09 [P < 0.001] and ß = -0.145 [P < 0.001]) were independent predictors of osteocalcin in premenopausal and postmenopausal women. Triglyceride levels were also independently associated with osteocalcin levels in premenopausal women (ß = -0.004 [P < 0.013]). The odds ratio (OR) for MetS was significantly higher in the lowest quartile than in the highest quartile of serum osteocalcin levels after adjusting for age, alkaline phosphatase, uric acid, high sensitivity C-reactive protein, and body mass index in all women (OR, 2.00; 95% confidence interval [CI], 1.49-2.68) as well as in premenopausal (OR, 2.23; 95% CI, 1.39-3.58) and postmenopausal (OR, 2.01; 95% CI, 1.26-3.23) subgroups. CONCLUSION: Lower serum osteocalcin concentrations were significantly associated with MetS in both premenopausal and postmenopausal women and were therefore independent of menopausal status.


Asunto(s)
Síndrome Metabólico/diagnóstico , Osteocalcina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Hemoglobina Glucada/análisis , Humanos , Persona de Mediana Edad , Posmenopausia , Premenopausia , Análisis de Regresión , República de Corea , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto Joven
4.
Transl Cancer Res ; 13(8): 4231-4241, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39262483

RESUMEN

Background: Tumor necrosis factor receptor 2 (TNFR2) is a subtype of the tumor necrosis factor receptors and is known to promote cancer progression by enhancing cancer cell proliferation and inducing immune suppression. More recently, there are reports that TNFR2 expression is related to the prognosis of patients with cancer, including lung, breast, esophageal, colorectal cancer, and lymphoma. In this study, the correlation between the expression of TNFR2 and the prognosis and clinicopathological factors of cancer was systematically evaluated. This study aimed at elucidating the relationship between TNFR2 and prognosis in patients with cancer. Methods: PubMed, Embase, and Cochrane Library were searched and a meta-analysis was performed to assess the prognostic and clinicopathological values of TNFR2 expression in patients with cancer. Results: Nine studies with 2,229 patients were included. High expression of TNFR2 was significantly correlated with poor overall survival (OS) [hazard ratio (HR), 1.76; 95% confidence interval (CI): 1.37-2.27; P<0.001] and disease-free survival (DFS) (HR, 2.75; 95% CI: 1.92-3.92; P<0.001). High expression of TNFR2 was also significantly associated with higher tumor grade [odds ratio (OR), 1.58; 95% CI: 1.26-1.98; P<0.001], higher tumor stage (OR, 2.41; 95% CI: 1.62-3.60; P<0.001) and higher clinical stage (OR, 1.80; 95% CI: 1.44-2.23; P<0.001). Conclusions: High expression of TNFR2 was related to poor prognosis and could be a prognostic factor in patients with cancer.

5.
Transl Cancer Res ; 13(9): 4913-4922, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39430827

RESUMEN

Background: There is growing evidence that long non-coding RNA long iatrogenic non-protein-coding RNA p53-induced transcript (LINC-PINT) is highly expressed in cancer tissue and is associated with the prognosis of cancer patients. The present study systematically analyzed the prognostic significance of LINC-PINT expression in cancer patients. We aimed to reveal the association between LINC-PINT expression and survival in cancer patients. Methods: We collected eligible studies through the PubMed, Embase, and Cochrane library searches until February 1, 2024. We collected the following data from the enrolled studies: first author, publication year, country, cancer type, case number, cancer stage, detection method and cut-off value of LINC-PINT expression, follow-up period, and survival outcome. The prognostic significance of LINC-PINT expression was evaluated by conducting a meta-analysis. StataSE17 (Stata, College Station, TX, USA) was used for all analyses. Results: Eleven eligible studies with 2,876 cancer patients were collected. The pooled results revealed that LINC-PINT expression was associated with favorable overall survival (OS) and disease-free survival (DFS) in cancer patients [for OS, hazard ratio (HR) =0.72, 95% confidence interval (CI): 0.64-0.80, P<0.001; for DFS, HR =0.70, 95% CI: 0.60-0.82, P<0.001]. Conclusions: LINC-PINT expression was associated with favorable OS and DFS, and it may serve as a valuable prognostic marker in cancer patients.

6.
Korean J Fam Med ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38773693

RESUMEN

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Methods: Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (√) of baseline and follow-up coronary artery calcium scores (CACSs) (Δ√transformed CACS). To adjust for differences in follow-up periods, Δ√transformed CACS was divided by the follow- up period (in years). Results: Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δ√transformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δ√transformed CACS analysis yielded no significant results. Conclusion: This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.

7.
Curr Med Imaging ; 19(7): 784-787, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36437728

RESUMEN

BACKGROUND: Diffuse large B-cell lymphomas are the most common type of non-Hodgkin lymphoma. Because cutaneous lymphomas predominantly originate from the T cells, primary cutaneous diffuse large B-cell lymphomas are considered a rare subtype of extranodal diffuse large B-cell lymphomas that commonly involve the subcutaneous tissues of the trunk and extremities. To date, only a single case of facial primary cutaneous diffuse large B-cell lymphoma has been reported in the literature. CASE REPORT: We present a case of primary cutaneous diffuse large B-cell lymphoma presented with a small painless nodule in the right nasolabial fold that had persisted for 10 days in a 67-year-old man. Ultrasonographic findings of this lesion mimicked the features of a complicated epidermal inclusion cyst. Primary cutaneous diffuse large B-cell lymphoma was confirmed by an excisional biopsy of the mass. CONCLUSION: The diagnosis of primary cutaneous diffuse large B-cell lymphomas presenting as "oops lesions" in daily clinical practice can be challenging due to their rarity and nonspecific clinical and radiological findings. Therefore, clinical suspicion and awareness are critical for the accurate diagnosis and management of patients with palpable soft tissue masses in the head and neck region.


Asunto(s)
Linfoma de Células B Grandes Difuso , Neoplasias Cutáneas , Masculino , Humanos , Lactante , Surco Nasolabial/diagnóstico por imagen , Surco Nasolabial/patología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen
8.
Transl Cancer Res ; 11(6): 1587-1594, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35836531

RESUMEN

Background: Ephrin receptor-A1 (EPHA1) participates in various developmental processes by engaging in cell adhesion, migration, and tissue boundary formation. EPHA1 is also associated with cancer progression and poor prognosis. However, the results of individual studies were inconsistent. Therefore, we aimed to systematically evaluate the association between survival and EPHA1 expression in patients with cancer. Methods: We searched electronic databases including PubMed, Embase, Scopus, and the Cochrane library until February 8, 2022. The pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated to explore the relationship between EPHA1 expression and survival in patients with cancer. Funnel plots and Egger's regression tests were conducted to evaluate publication bias, and sensitivity analysis was performed to determine the reliability of the pooled results. Results: Eight studies with 1079 cancer patients were enrolled. EPHA1 expression was associated with progression-free survival (PFS) (HR 1.79, 95% CI: 1.49-2.15, P<0.001). EPHA1 expression was also associated with poor overall survival (HR 2.23, 95% CI: 1.42-3.51, P<0.001), higher tumor stage [odds ratio (OR) 1.74, 95% CI: 1.15-2.61, P=0.008], and lymph node metastasis (OR 1.88, 95% CI: 1.24-2.87, P=0.003) in patients with gastric cancer. Discussion: EPHA1 expression was significantly associated with PFS in patients with cancer.

9.
Dis Markers ; 2022: 8567642, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35265227

RESUMEN

Background: Recent studies have shown that nicotinamide adenosine dinucleotide phosphate oxidase 4 (NOX4) is related to cancer development, proliferation, invasion, epithelial-to-mesenchymal transition, and metastasis. The prognostic value of NOX4 expression although has been reported in various cancers, it remains unclear as several studies have reported conflicting results. Therefore, the purpose of this study was to systematically investigate the prognostic value of NOX4 expression in cancer patients. Method: Appropriate studies were collected by searching the PubMed, EMBASE, and Cochrane library databases, and the prognostic value of NOX4 expression in cancer patients was assessed through a meta-analysis. Results: Nine eligible studies involving 2675 cancer patients were included in this meta-analysis. We found that NOX4 expression is related to prognosis in cancer patients. In particular, high expression of NOX4 was significantly associated with overall survival in patients with gastrointestinal cancer (hazard ratio [HR]: 1.83, 95% confidence interval [CI]: 1.39-2.42, p < 0.001). Conclusion: NOX4 expression is significantly correlated with overall survival in patients with gastrointestinal cancer, indicating that it could be a potential prognostic marker.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , NADPH Oxidasa 4/biosíntesis , Neoplasias/metabolismo , Humanos , Neoplasias/mortalidad , Pronóstico , Tasa de Supervivencia
10.
J Pathol Transl Med ; 56(4): 199-204, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35535365

RESUMEN

BACKGROUND: Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis. METHODS: We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated. RESULTS: Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors. CONCLUSIONS: Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

11.
Medicine (Baltimore) ; 100(11): e25006, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725975

RESUMEN

BACKGROUND: It has been revealed that CD109 expression is associated with prognosis in cancer patients, but it remains unclear thus far. Therefore, we performed a meta-analysis in the present study for a better assessment of the prognostic role of CD109 expression in cancer patients. METHODS: Eligible studies were collected through a search of the PubMed, Embase, Cochrane Library, and Scopus databases. The pooled hazard ratio (HR) with 95% confidence interval (CI) was evaluated to reveal the association between CD109 expression and overall survival (OS) in cancer patients. RESULTS: Seven studies with 1583 patients were enrolled. The pooled HR with 95% CI was calculated as 2.31 (95% CI 1.93-2.76, P < .001), suggesting an association between high expression of CD109 and unfavorable OS in cancer patients. CONCLUSION: This analysis indicated that CD109 expression could be used as a prognostic biomarker in cancer patients. This is the first meta-analysis to report the relationship between CD109 expression and prognosis in cancer patients.


Asunto(s)
Antígenos CD/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Proteínas Ligadas a GPI/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Adulto Joven
12.
Transl Cancer Res ; 10(7): 3225-3235, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35116629

RESUMEN

BACKGROUND: The expression of S100A8 and S100A9 is found to be related with the survival of cancer patients, but the results and information regarding their prognostic significance are inconsistent in literature. This study, therefore, aimed to perform a comprehensive meta-analysis and determine the prognostic significance of S100A8 and S100A9 expression in patients with cancer. METHODS: Data were collected by performing a literature search on the PubMed, Cochrane library, and Scopus databases. Pooled hazard ratio (HR) with confidence interval (CI) was calculated to assess the correlation between S100A8 and S100A9 expression and survival in patients with cancer. RESULTS: In total, 5 studies that enrolled 735 cancer patients were included in the meta-analysis. The pooled HR concerning S100A8 and S100A9 expression was 1.98 (95% CI: 1.20-3.29, P=0.008) for disease-free survival (DFS), indicating an association between high expression of S100A8 and S100A9 and poor DFS in cancer patients. However, the expression of S100A8 and S100A9 was not significantly correlated with disease-specific survival (HR 1.71, 95% CI: 0.86-3.40, P=0.128). DISCUSSION: The current meta-analysis revealed that S100A8 and S100A9 expression may be a potential prognosticator of DFS in cancer patients. The present systematic review is the first to investigate the survival outcomes of cancer patients with S100A8 and S100A9 expression.

13.
Transl Cancer Res ; 10(7): 3356-3363, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35116641

RESUMEN

BACKGROUND: Recent studies have shown that CD90 has an important role in cancer development. Moreover, CD90 is reportedly associated with cancer progression, metastasis, and poor prognosis. Thus, we performed this meta-analysis to investigate the prognostic and clinicopathological value of CD90 expression in patients with cancer. METHODS: Eligible studies were collected by searching PubMed, Embase, and the Cochrane library. The pooled results were analyzed to reveal the association between CD90 expression and survival as well as the clinicopathological characteristics of cancer patients. RESULTS: CD90 overexpression was associated with poor survival in cancer patients [for overall survival, hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.42-4.62, P=0.002; for disease-free survival, HR: 1.88, 95% CI: 1.08-3.27, P=0.025] and was also significantly correlated with a larger tumor size [odds ratio (OR): 1.97, 95% CI: 1.01-3.85, P=0.048), higher tumor grade (OR: 2.72, 95% CI: 1.33-5.54, P=0.006), lymph node metastasis (OR: 3.66, 95% CI: 1.14-11.78, P=0.029), and higher tumor-node-metastasis stage (OR: 4.79, 95% CI: 2.28-10.04, P<0.001). CONCLUSIONS: CD90 overexpression could predict poor prognosis and may hence be a potential prognostic biomarker for cancer patients.

14.
Transl Cancer Res ; 10(3): 1449-1456, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35116470

RESUMEN

BACKGROUND: CXC chemokine receptor 3 (CXCR3) plays a critical role in tumorigenesis, and CXCR3 expression is associated with prognosis in many cancers. Recently, CXCR3 expression is recognized as a potential prognostic factor for patients with gastric cancer. In this study, we analyzed the prognostic significance of CXCR3 expression in gastric cancer. METHODS: We conducted a meta-analysis after selecting eligible studies through a literature search. We calculated pooled results to assess the associations between CXCR3 expression and overall survival (OS) and clinicopathological factors for gastric cancer. RESULTS: The pooled hazard ratio (HR) with 95% confidence interval (CI) between high expression of CXCR3 and OS was 0.46 (95% CI 0.30-0.71, P<0.001), suggesting that high expression of CXCR3 was associated with a favorable OS. High expression of CXCR3 was significantly correlated with younger age [odds ratio (OR) 0.67, 95% CI: 0.49-0.91, P=0.011], lower tumor grade (OR 0.46, 95% CI: 0.29-0.73, P=0.001), absence of lymph node metastasis (OR 0.47, 95% CI: 0.31-0.71, P<0.001), and lower Tumor-Node-Metastasis stage (OR 0.51, 95% CI: 0.35-0.74, P<0.001). CONCLUSIONS: High expression of CXCR3 was associated with better survival and may be a potential prognostic factor for patients with gastric cancer patients.

15.
Pan Afr Med J ; 40: 181, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35059101

RESUMEN

Ectopic adrenal gland in the ovary is very rare case, and even more rarer in older women. We reported a case of ectopic adrenal tissue as an incidental finding in left ovary from a 68-year-old woman. She presented with bearing down sensation due to uterine prolapse for 5 years. Upon physical examination, uterine prolapse grade III, cystocele, and rectocele were observed. Ultrasonography findings showed 0.69 cm intramural myoma, and no specific findings were found in the bilateral adnexae. She underwent a total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and anterior-posterior repair. The final pathologic diagnosis of the case was ectopic adrenal gland tissue in the left ovary and uterine leiomyoma. No eventful reactions were observed during hospitalization and after discharge. Although ectopic adrenal gland rarely occurs in elderly women and in the pelvic ovaries, it has a risk of neoplastic transformation and accompanying germ cell tumor and sex cord tumor. Hence, if the ectopic adrenal gland tissue is suspected during surgery, the tissue should be removed. Additionally, by closely examining the contralateral ovary, determining whether other lesions are suspected is necessary. If the other lesions including germ cell tumor or sex cord tumor are suspected, a biopsy of the contralateral ovarian tissue should be performed. Thus, gynecologists must have knowledge about ectopic adrenal gland tissues.


Asunto(s)
Leiomioma , Ovario , Glándulas Suprarrenales , Anciano , Femenino , Humanos , Histerectomía , Salpingooforectomía
16.
Pathol Res Pract ; 218: 153336, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33450435

RESUMEN

Cancer stem cells (CSCs) are believed to be responsible for tumor growth, invasion, and metastasis. Submucosal invasion, which greatly enhances metastasis risk, is a critical step in gastric cancer (GC) progression. To identify stem cell-related markers associated with submucosal invasion and lymph node (LN) metastasis in GCs, we investigated the expression of candidate CSC markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs that manifested submucosal invasion. We discovered that EPHB2 and LGR5 expression was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer, and the proportion of stem cell marker-positive cells substantially increased during submucosal invasion. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. Unexpectedly, no CSC markers showed any associations with LN metastasis, and only loss of EPHB2 expression was associated with increased LN metastasis. Treatment of RSPO2, a niche factor, along with Wnt 3a, to GC cells led to increased EPHB2 and LGR5 mRNA levels. RNA in situ hybridization confirmed specific RSPO2 expression in the smooth muscle cells of the muscularis mucosa, suggesting that RSPO2 is responsible for the increased expression of ISC markers in GC cells at the basal areas. In summary, no stem cell markers were associated with increased LN metastasis in early GCs. Conversely, isolated EPHB2 expression was associated with lower LN metastasis. EPHB2 and LGR5 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs, which was induced by a niche factor, RSPO2, from the muscularis mucosa.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Movimiento Celular , Mucosa Intestinal/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias Gástricas/metabolismo , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Células Madre Neoplásicas/patología , Receptor EphB2/genética , Receptor EphB2/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Estudios Retrospectivos , Transducción de Señal , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología
17.
Sci Rep ; 11(1): 17750, 2021 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493772

RESUMEN

Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no ß-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.


Asunto(s)
Mama/metabolismo , Células Epiteliales/metabolismo , Proteínas de Neoplasias/biosíntesis , Receptores Acoplados a Proteínas G/biosíntesis , Neoplasias de la Mama Triple Negativas/metabolismo , Adulto , Anciano , Mama/citología , Mama/fisiología , Enfermedades de la Mama/genética , Enfermedades de la Mama/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/metabolismo , Femenino , Fibroadenoma/genética , Fibroadenoma/metabolismo , Humanos , Hibridación in Situ , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Papiloma Intraductal/genética , Papiloma Intraductal/metabolismo , Tumor Filoide/genética , Tumor Filoide/metabolismo , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Receptores Acoplados a Proteínas G/genética , Regeneración/genética , Neoplasias de la Mama Triple Negativas/genética
18.
Medicine (Baltimore) ; 99(32): e21575, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32769903

RESUMEN

BACKGROUND: Recent studies showed that Macrophage migration inhibitory factor (MIF) is overexpressed and closely associated with prognosis in cancer patients. The present study was systematically evaluated the prognostic significance of MIF expression in cancer patients. METHODS: PubMed, Cochrane library and Scopus were searched for eligible studies up to January 2020. Pooled hazard ratio with confidence interval (CI) was determined to assess the relationship between MIF expression and survival in cancer patients. RESULTS: A total of 8 studies comprising 847 cancer patients were included in this meta-analysis. For overall survival, the pooled hazard ratio was 2.23 (95% CI 1.67-2.99, P < .001). For disease-free survival, the pooled hazard ratio was 2.24 (95% CI 1.69-2.96, P < .001). The results suggested that high expression of MIF was significantly related to poor overall survival and disease-free survival in cancer patients. CONCLUSION: MIF expression could be a valuable prognostic factor in cancer patients.


Asunto(s)
Factores Inhibidores de la Migración de Macrófagos/análisis , Neoplasias/sangre , Pronóstico , Distribución de Chi-Cuadrado , Expresión Génica/fisiología , Humanos , Oxidorreductasas Intramoleculares/análisis , Oxidorreductasas Intramoleculares/sangre , Oxidorreductasas Intramoleculares/fisiología , Factores Inhibidores de la Migración de Macrófagos/sangre , Factores Inhibidores de la Migración de Macrófagos/fisiología , Neoplasias/fisiopatología
19.
In Vivo ; 34(5): 2209-2215, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32871743

RESUMEN

BACKGROUND: CD63 has been described as a key factor in extracellular vesicle production and endosomal cargo sorting, and there have been certain reports suggesting an association between CD63 expression and survival in patients with tumors including gastric, colon and lung cancer. However, the prognostic value of CD63 expression remains contradictory. Hence, we performed this meta-analysis to assess the prognostic value of CD63 expression in solid tumors. MATERIALS AND METHODS: Eligible studies were collected by searching the PubMed, Embase and Cochrane libraries. The hazard ratio (HR) with 95% confidence interval (CI) were evaluated to reveal the association between CD63 expression and survival in solid tumors. RESULTS: Five studies with a total of 1,454 patients were included. The HR evaluating CD63 expression on survival was 1.34 (95%CI=0.92-1.97, p=0.129). In subgroup analysis, the HRs of lung cancer and other tumors were 0.50 (95% CI=0.32-0.77, p=0.002) and 2.16 (95% CI=1.93-2.42, p<0.001) respectively. CD63 expression was significantly associated with poor disease-specific survival (HR=1.69, 95% CI=1.15-2.49, p=0.008), but not with disease-free survival and overall survival. Also, there was a significant association between CD63 expression with poor survival in the group of sample size more than 150 patients (HR=2.15, 95% CI=2.92-2.41, p<0.001), but not in the group of sample size with fewer than 150 patients. CONCLUSION: This meta-analysis suggested that CD63 expression may be a potential prognostic marker in solid tumors.


Asunto(s)
Neoplasias , Supervivencia sin Enfermedad , Humanos , Neoplasias/genética , Pronóstico , Modelos de Riesgos Proporcionales , Tetraspanina 30/genética
20.
Sci Rep ; 10(1): 14136, 2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32839520

RESUMEN

Rab27 is an essential molecule of vesicle fusion and trafficking in exosome secretion process, which plays important roles in cancer progression and metastasis. Recent studies reported that Rab27 expression is also associated with cancer prognosis. Therefore, we performed a meta-analysis to reveal the prognostic significance of Rab27 expression in solid cancer. Data were extracted by searching on PubMed, Embase and Cochrane library until February 15 2020. Pooled hazard ratio (HR) with confidence interval (CI) was calculated to evaluate the association between Rab27 expression and survival in solid cancer. Ten studies with 1434 cancer patients were including for this meta-analysis. High expression of Rab27 was associated with poor survival (HR 2.67, 95% CI 1.52-4.69, p = 0.001). High expression of Rab27A was significantly associated with lymph node metastasis (HR 1.53, 95% CI 1.00-2.34, p = 0.048). High expression of Rab27B was significantly correlated with lymph node and distant metastasis (HR 2.15, 95% CI 1.56-2.95, p < 0.001; HR 6.80, 95% CI 3.12-14.85, p < 0.001), and higher TNM stage (HR 2.55, 95% CI 1.78-3.65, p < 0.001). This meta-analysis revealed that Rab27 expression could be a potential prognostic marker in solid cancer.


Asunto(s)
Metástasis Linfática/patología , Neoplasias/patología , Proteínas de Unión al GTP rab/metabolismo , Proteínas rab27 de Unión a GTP/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Metástasis Linfática/genética , Estadificación de Neoplasias , Neoplasias/mortalidad , Pronóstico , Proteínas de Unión al GTP rab/genética , Proteínas rab27 de Unión a GTP/genética
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