CD63 and GLUT-1 Overexpression Could Predict a Poor Clinical Outcome in GIST: A Study of 54 Cases with Follow-Up

Lewitowicz, Piotr; Matykiewicz, Jarosław; Kozieł, Dorota; Chrapek, Magdalena; Horecka-Lewitowicz, Agata; Głuszek, Stanisław

doi:10.1155/2016/6478374

Cited by 14 publications

(17 citation statements)

References 30 publications

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“…Moreover, CD63 may execute metastasis-promoting functions as a receptor of tissue inhibitor of metalloproteinases interacting with β1 integrins (10). Furthermore, certain studies have revealed that CD63 expression is correlated with a tumor progression and lower survival (3,6,8,(15)(16)(17). Thus, we performed this meta-analysis to better understand the prognostic value of CD63 expression in solid tumors.…”

Section: Discussionmentioning

confidence: 99%

“…We identified 5 eligible studies with 1,454 patients for this meta-analysis. Kaprio et al, Miki et al and Lewitowicz at al. reported that positive or high expression of CD63 was associated with poor prognosis in colorectal cancer, gastric cancer and gastrointestinal stromal tumor respectively (3,6,8). On the other hand, Kown et al and Koh et al showed that negative or low expression of CD63 was correlated with a poor survival in lung adenocarcinoma and non-small cell lung cancer respectively (5,7).…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Value of CD63 Expression in Solid Tumors: A Meta-analysis of the Literature

Koh

Jang

Kim

2020

In Vivo

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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 metaanalysis suggested that CD63 expression may be a potential prognostic marker in solid tumors. Exosomes are small membrane-bound vesicles that are released from various cells into the extracellular spaces (1, 2). Such vesicles contain proteins, lipids and nucleic acids, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells (1, 2). Recently, it has been reported that exosomes from tumor cells might be involved in tumor progression by modulating the tumor microenvironment, e.g. metastatic niche formation and angiogenesis (3). The tetraspanin protein CD63 has been described as a key factor in extracellular vesicle production and endosomal cargo sorting, and there have been reports evaluating the association between CD63 expression and tumor existense (4). Moreover, some studies have suggested that CD63 expression is associated with survival in patients with tumors (3, 5-8). However, the prognostic value of CD63 expression remains contradictory or inconclusive. Hence, we conducted this meta-analysis to investigate the prognostic value of CD63 expression in solid tumors. Materials and Methods Literature search. We performed a literature search in PubMed, Embase and Cochrane library up to March 15, 2020 using the following terms: (CD63) and (cancer or tumor or carcinoma or neoplasm or malignancy) and (prognostic or predict or prognosis or survival or outcome). All articles were screened for exclusion and review articles were screened to find eligible studies. Inclusion and exclusion criteria. Inclusion criteria for this study were as follows: (i)...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic Value of CD63 Expression in Solid Tumors: A Meta-analysis of the Literature

Koh

Jang

Kim

2020

In Vivo

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“…In light of Miettinen's classification, Ki-67 could become a promising biomarker. Our experience has taught us to keep a distance from prediction based on MC in cases when just a small biopsy had been taken; thus, we previously tried to focus our attention on other biomarkers [ 26 , 31 – 34 ]. In a very recent paper by Liu et al covering 1022 patients, the cut-off values were stated at 6% which is very close our data, although some methodological differences exist between us [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…This study has been a natural continuation of our previously published research concerning the significance and the usefulness of GLUT-1, CD9, and CD63 in GIST. The inclusion criteria were previously described in detail [ 26 ]. There was no selection bias.…”

Section: Methodsmentioning

confidence: 99%

Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors

et al. 2018

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Background Technological advances constantly provide cutting-edge tools that enhance the progress of diagnostic capabilities. Gastrointestinal stromal tumors belong to a family of mesenchymal tumors where patient triaging is still based on traditional criteria such as mitotic count, tumor size, and tumor location. Limitations of the human eye and randomness in choice of area for mitotic figure counting compel us to seek more objective solutions such as digital image analysis. Presently, the labelling of proliferative activity is becoming a routine task amidst many cancers. The purpose of the present study was to compare the traditional method of prediction based on mitotic ratio with digital image analysis of cell cycle-dependent proteins. Methods Fifty-seven eligible cases were enrolled. Furthermore, a digital analysis of previously performed whole tissue section immunohistochemical assays was executed. Digital labelling covered both hotspots and not-hotspots equally. Results We noted a significant diversity of proliferative activities, and consequently, the results pointed to 6.5% of Ki-67, counted in hotspots, as the optimal cut-off for low–high-grade GIST. ROC analysis (AUC = 0.913; 95% CI: 0.828–0.997, p < 0.00001) and odds ratio (OR = 40.0, 95% CI: 6.7–237.3, p < 0.0001) pointed to Ki-67 16% as the cut-off for very high-grade (groups 5–6) cases. With help of a tumor digital map, we revealed possible errors resulting from a wrong choice of field for analysis. We confirmed that Ki-67 scores are in line with the level of intracellular metabolism that could be used as the additional biomarker. Conclusions Tumor digital masking is very promising solution for repeatable and objective labelling. Software adjustments of nuclear shape, outlines, size, etc. are helpful to omit other Ki-67-positive cells especially small lymphocytes. Our results pointed to Ki-67 as a good biomarker in GIST, but concurrently, we noted significant differences in used digital approaches which could lead to unequivocal results.

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“…have reported that urine samples from prostate cancer patients included CD63-positive exosomes[ 7 ]. In addition, CD63 expression has been reported to be a prognostic factor in patients with gastrointestinal stromal tumor[ 8 ]. However, the significance of CD63 in patients with gastric cancer has not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Clinico-pathological significance of exosome marker CD63 expression on cancer cells and stromal cells in gastric cancer

et al. 2018

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BackgroundIt has been reported that CD63, an exosome marker, is expressed in solid cancer tissues. However, its significance in patients with gastric cancer has not been clarified. Exosomes derived from cancer cells and stromal cells might play an important role in the intracellular communications involved in the development of carcinoma. This study aimed to clarify the relationship between CD63 expression in cancer cells and stromal cells and clinical-pathologic factors.MethodsA total of 595 gastric cancer patients were enrolled in this study. CD63 expression in cancer cells and stromal cells was analyzed by immunohistochemistry. The correlations between CD63 expression and several clinicopathological factors were investigated.ResultsCD63 expression was mainly observed on the cell membranes of cancer cells, and in the cytoplasm of stromal cells. Of 595 patients, 247 cases had CD63-positive cancer cells, and 107 cases had CD63-positive stromal cells. Cases with CD63-positive cancer cells were significantly correlated with scirrhous-type gastric cancer, tumor depth, lymph node metastasis, lymphatic invasion, and tumor size. Cases with CD63-positive stromal cells were significantly correlated with age (≥65), tumor depth (T3-4), lymphatic invasion, and tumor size (≥ 5 cm). The 5-year survival rate was significantly lower (p<0.001) in patients with CD63-positive than CD63-negative tumors. Multivariate analysis showed that CD63 expression in cancer cells was a significant independent prognostic factor in patients with gastric cancer.ConclusionCD63 might be a prognostic marker for patients with gastric cancer. CD63-positive exosomes might be associated with the interaction between stromal cells and cancer cells.

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CD63 and GLUT-1 Overexpression Could Predict a Poor Clinical Outcome in GIST: A Study of 54 Cases with Follow-Up

Cited by 14 publications

References 30 publications

Prognostic Value of CD63 Expression in Solid Tumors: A Meta-analysis of the Literature

Prognostic Value of CD63 Expression in Solid Tumors: A Meta-analysis of the Literature

Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors

Clinico-pathological significance of exosome marker CD63 expression on cancer cells and stromal cells in gastric cancer

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