Expression and Prognostic Impact of VEGF, CD31 and αSMA in Resected Primary Lung Cancers

Usuda, Katsuo; Iwai, Syun; Funasaki, Aika; Sekimura, Atsushi; Motono, Nozomu; Ueda, Y.; Shimazaki, M; Uramoto, Hidetaka

doi:10.21873/anticanres.12695

Cited by 8 publications

(8 citation statements)

References 18 publications

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“…This result is in keeping with that reported by El-Gohary et al in prostatic adenocarcinoma tissues [45]. However, several other studies on different types of cancer showed no association between the two proteins [8,35,46,47]. Our result indicates a possible contribution of VEGF-A in microvessel formation, but further studies with larger sample size are required to determine the type of the relationship between VEGF-A and CD31 in NSCLC in order to have a clearer insight into the related angiogenesis pathway.…”

Section: Discussionsupporting

confidence: 92%

“…Our statistical analysis showed higher staining scores of VEGF-A, CD31 and GRP78 in adenocarcinoma compared with squamous cell carcinoma (p-value < 0.001, p-value = 0.001, and p-value = 0.045, respectively). The positive correlation between VEGF-A expression and adenocarcinoma was previously revealed in many studies [32][33][34][35]. On the other hand, other researchers could not come out with the same conclusion neither for CD31 [8,[35][36][37][38].…”

Section: Discussionmentioning

confidence: 88%

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Expression Profiles of VEGF-A, CD31 and GRP78 in Non-Small Cell Lung Cancer.

Al-Keilani¹,

Alqudah²,

Almomani³

et al. 2020

Preprint

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BackgroundAngiogenesis is mandatory for tumor growth and progression. The modest response to the anti-angiogenic therapies in non-small cell lung cancer reflects the presence of confounding molecular factors. The aims of this study were to investigate the expression levels of VEGF-A, CD31 and GRP78 and test for significant correlations between them.MethodsParaffin-embedded NSCLC tissue samples (71 adenocarcinoma and 23 squamous cell carcinoma) were retrospectively collected from 94 patients who underwent surgical resection between 2008 and 2015; and did not receive chemotherapy or radiotherapy prior to surgery. The expressions of VEGF-A, CD31 and GRP78 were determined by immunohistochemistry. ResultsHigh expression levels of VEGF-A, CD31 and GRP78 were observed in 15, 36 and 74 cases, respectively. Adenocarcinomas expressed higher levels of the aforementioned proteins as compared with squamous cell carcinomas (p-value < 0.05). Moreover, a statistically significant association was found between VEGF-A and CD31 expression levels (p-value = 0.006).ConclusionsOur study was the first to investigate the associations between GRP78 and the angiogenesis markers CD31 and VEGF-A in NSCLC patients. High GRP78 expression was revealed in the majority of the investigated samples. Nevertheless, no relationship was found between GRP78 and VEGF-A or CD31 which could be attributed to small sample size. On the other hand, the positive association between VEGF-A and CD31 expression levels suggests that VEGF-A may cooperate with CD31 to promote angiogenesis in NSCLC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 88%

Expression Profiles of VEGF-A, CD31 and GRP78 in Non-Small Cell Lung Cancer.

Al-Keilani¹,

Alqudah²,

Almomani³

et al. 2020

Preprint

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“…VEGF, a powerful angiogenic agent in neoplastic tissues, has been widely studied in the field of neoplastic vascularization (14). Previous researches had confirmed the expression of VEGF was increased in many cancers, including colon cancer (15), lung cancer (16), breast cancer (17), and gastric cancer (18), which indicated the poor survival for patients. Bevacizumab, a recombinant humanized monoclonal antibody to VEGF and known by its brand name, Avastin®, blocks tumor cell-derived VEGF-A, impairing the development of new vessels and leading to tumor starvation and, consequently, growth inhibition (19).…”

Section: Discussionmentioning

confidence: 96%

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition

Zhang

Chen

et al. 2019

Front. Immunol.

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The AURELIA trial demonstrated that adding Bevacizumab to chemotherapy significantly improved progression-free survival (PFS) for platinum resistant recurrent ovarian cancer. Recently, immunotherapy also presented potential anti-tumor effects in several malignant solid tumors. This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing <6 months after completing platinum-based therapy. Based on responding to at least 2 cycles of Bevacizumab-containing chemotherapy (BC), these Patients were divided into BC response group and BC non-response group. Immunohistochemistry was used to detect that PD-L1 expression and tumor angiogenesis-related proteins (VEGF and Semaphorin4D) in tissues from 124 patients with CREOC. The positive expressions of PD-L1, VEGF, and Semaphorin4D (SEMA4D) were found in 58.73, 50.79, and 71.43% of the 63 cases CREOC tissues with BC response, respectively, which were significantly higher than that in the 61 cases BC non-response group ( P < 0.05). PD-L1 expression correlated with SEMA4D and VEGF positively ( r = 0.344 and 0.363, P < 0.001). Over-expressions of PD-L1, VEGF and SEMA4D are associated with more malignant clinicopathologic characteristics of CREOC Patients. In survival analysis, patients' response to BC was the independent factor for evaluation of PFS and overall survival (OS). Cell functional assays showed that Atezolizumab in combination with Bevacizumab inhibited the proliferation, migration, and invasion of cisplatin resistant ovarian cancer cell line A2780cis in vitro synergistically, which maybe associate with Bevacizumab suppressing the epithelial-mesenchymal transition (EMT) and PD-L1 expression by targeting STAT3. Furthermore, Bevacizumab and Atezolizumab induced synergistic anti-tumor effect in vivo . These findings suggest a novel therapeutic strategy for cisplatin resistant recurrent EOC and its mechanism warrants further study.

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“…As a marker of angiogenesis, these findings potentially show the presence of increased angiogenesis within the Bladder tumours. The scoring system used in this research examines both staining intensity and percentage positivity in tumour cells and has been used by others [27].…”

Section: Discussionmentioning

confidence: 99%

The role of antibody expression and their association with bladder cancer recurrence: a single-centre prospective clinical-pilot study in 35 patients

et al. 2020

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Background Bladder cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases annually. About 75–85% of BC are non-muscle invasive (NMIBC), which is associated with high recurrence and progression rates (50–60% within 7–10 years). There are no routine biomarkers currently available for identifying BC patients at increased risk of developing recurrence. The focus of this research study was to evaluate antibody expression in BC patients and their association with cancer recurrence. Methods 35 patients scheduled for TURBT were recruited after written informed consent. Ethical approval for the project was granted via IRAS (REC4: 14/WA/0033). Following surgical procedure, tissues were preserved in 10% buffered formalin and processed within 24 h in FFPE blocks. 7 sections (4 µm each) were cut from each block and stained for CD31, Human epidermal growth factor receptor-2 (HER-2), S100P, Cyclooxygenase-2 (COX-2), VEGFR-3 thrombomodulin and CEACAM-1 using immunohistochemistry. Clinical outcome measures (obtained via cystoscopy) were monitored for up to 6 months following surgical procedure. Results There was significantly increased expression of CD31 (p < 0.001), HER-2 (p = 0.032), S100P (p < 0.001), COX-2 (p < 0.001), VEGFR-3 (p < 0.001) and decreased expression of thrombomodulin (p = 0.010) and CEACAM-1 (p < 0.001) in bladder tumours compared to normal bladder tissues. HER-2 expression was also significantly associated with cancer grade (p = 0.003), especially between grade 1 and grade 2 (p = 0.002) and between grade 1 and grade 3 (p = 0.004). There was also a significant association between cancer stage and HER-2 expression (p < 0.001). Although recurrence was significantly associated with cancer grade, there was no association with antibody expression. Conclusion Findings from the present study may indicate an alternative approach in the monitoring and management of patients with BC. It is proposed that by allowing urological surgeons access to laboratory markers such as HER-2, Thrombomodulin and CD31 (biomarker profile), potentially, in the future, these biomarkers may be used in addition to, or in combination with, currently used scoring systems to predict cancer recurrence. However, verification and validation of these biomarkers are needed using larger cohorts.

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Expression and Prognostic Impact of VEGF, CD31 and αSMA in Resected Primary Lung Cancers

Abstract: Not the number of tumor vessels but their maturation may be a prognostic factor of patients with lung cancer. VEGF may not only stimulate proliferation of endothelial cells but also their maturation in differentiated lung cancers.

Cited by 8 publications

References 18 publications

Expression Profiles of VEGF-A, CD31 and GRP78 in Non-Small Cell Lung Cancer.

Expression Profiles of VEGF-A, CD31 and GRP78 in Non-Small Cell Lung Cancer.

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition

The role of antibody expression and their association with bladder cancer recurrence: a single-centre prospective clinical-pilot study in 35 patients

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