Relationship between expression and prognostic ability of PTEN, STAT3 and VEGF-C in colorectal cancer

Jin, Canhui; Wang, Aihong; Chen, Jianmin; Liu, Xiaomin; Wang, Gongping

doi:10.3892/etm.2012.651

Cited by 32 publications

(32 citation statements)

References 23 publications

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“…The results of our study also strongly suggest that VEGF-C expression in tumor tissue may be a good indicator of poor prognosis in ESCC patients. This association has also been found in previous studies examining VEGF-C expression and survival in patients with gastric and colorectal cancer [32,33]. …”

Section: Discussionsupporting

confidence: 60%

Vascular Endothelial Growth Factor-C Expression as a Biomarker of Poor Prognosis in Esophageal Squamous Cell Carcinoma: A Meta-Analysis

et al. 2015

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Background: Vascular endothelial growth factor C (VEGF-C) is involved in the development and progression of tumor angio-/lymphangiogenesis. The purpose of this study is to evaluate whether VEGF-C expression is an indicator of aggressiveness and poor prognosis of esophageal squamous cell carcinoma (ESCC). Method: A meta-analysis was conducted to investigate the association between VEGF-C expression with clinicopathological characteristics and survival of ESCC patients. The dataset was defined by searching PubMed, Embase, Google Scholar, and the Cochrane database for appropriate articles published until April 2014. Result: The final analysis was made from 9 studies, including 656 ESCC patients. Positive VEGF-C expression was defined by immunohistochemistry (IHC) or mRNA expression analysis. The results demonstrated that VEGF-C expression was significantly associated with advanced-stage disease (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.37-3.84, P = 0.002), deeper tumor invasion, lymph node metastasis, and lymphatic invasion. The 5-year survival of VEGF-C expression-negative patients was found to be better than that of VEGF-C expression-positive patients (OR = 0.35, 95% CI = 0.21-0.58, P < 0.0001). However, there was no significant association between the VEGF-C expression levels and either poorer tumor differentiation or vascular invasion. Conclusion: The results of the meta-analysis strongly indicate that VEGF-C expression could function as a marker for predicting the aggressiveness and prognosis of ESCC.

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Section: Discussionsupporting

confidence: 60%

Vascular Endothelial Growth Factor-C Expression as a Biomarker of Poor Prognosis in Esophageal Squamous Cell Carcinoma: A Meta-Analysis

et al. 2015

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“…Moreover the 3- and 5-years survival rates of patients normally expressing PTEN were significantly higher than those of patients with a PTEN-negative tumor (38). …”

Section: Prognostic Role Of Ptenmentioning

confidence: 89%

Functions and Regulation of the PTEN Gene in Colorectal Cancer

Molinari¹,

Frattini²

2014

Front. Oncol.

107

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Phosphatase and TENsin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene located at chromosome 10q23.31, encoding for a 403-amino acid protein that possesses both lipid and protein phosphatase activities. The main function of PTEN is to block the PI3K pathway by dephosphorylating phosphatidylinositol (PI) 3,4,5-triphosphate to PI-4,5-bisphosphate thus counteracting PI3K function. PTEN inactivation is a frequent event in many cancer types and can occur through various genetic alterations including point mutations, large chromosomal deletions, and epigenetic mechanisms. In colorectal cancer (CRC) PTEN is altered through mixed genetic/epigenetic mechanisms (typically: mutations and promoter hypermethylation or 10q23 LOH and promoter hypermethylation), which lead to the biallelic inactivation of the protein in 20–30% of cases. The role of PTEN as a prognostic and predictive factor in CRC has been addressed by relatively few works. This review is focused on the report and on the discussion of the studies investigating these aspects. Overall, at the moment, there are conflicting results and, therefore it has not been clarified whether PTEN might play a prognostic role in CRC. The same is valid also for the predictive role, leading to the fact that PTEN evaluation cannot be used in routinely diagnosis for the early identification of patients who might be addressed to the treatment with EGFR-targeted therapies, at odds with other genetic alterations belonging to EGFR-downstream pathways. The reason of discordant results may be attributable to several issues: (1) the size of the analyzed cohort, (2) patients inclusion criteria, (3) the methods of assessing PTEN alteration. In particular, there are no standardized methods to evaluate this marker, especially for immunohistochemistry, a technique suffering of intra and inter-observer variability due to the semi-quantitative character of such an analysis. In conclusion, much work, especially in large and homogeneous cohorts of cases from different laboratories, has to be done before the establishment of PTEN as prognostic or predictive marker in CRC.

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“…Clinically, elevated serum IL-6 has been associated with inferior survival in CRC 34 , and in a phase II study of rectal cancer patients treated with neoadjuvant bevacizumab and chemoradiation, change in plasma IL-6 correlated with degree of tumor regression 35 . Data regarding STAT3 have been less conclusive, with studies supporting both positive 36–38 and negative 39,40 prognostic roles for intratumoral STAT3 expression.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy

Matsusaka

Hanna

Cao

et al. 2016

Clinical Cancer Research

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Background The IL-6/STAT3 axis promotes inflammation, angiogenesis, and cancer. The effect of genetic variants within this pathway on benefit from anti-angiogenic cancer therapy is unknown. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in IL-6/STAT3 signaling can predict efficacy of bevacizumab-based chemotherapy in metastatic colorectal cancer (mCRC) patients Methods Associations between potentially functional IL-6 (rs2069837, rs1800795) and STAT3 (rs744166, rs4796793) SNPs and clinical outcomes (progression-free survival, overall survival and tumor response rate) were evaluated in mCRC patients receiving first-line FOLFIRI plus bevacizumab in two randomized phase III trials: TRIBE (n=223, training cohort) and FIRE-3 (n=288, validation cohort). Patients receiving FOLFIRI plus cetuximab in FIRE-3 (n=264) served as a control cohort. The interaction between genotype and primary tumor location with clinical outcomes was examined. Genomic DNA isolated from whole blood or tumor tissue was analyzed by PCR-based direct sequencing. Results Patients with an IL-6 rs2069837 G allele treated with FOLFIRI plus bevacizumab had an inferior PFS than those with the A/A genotype in TRIBE (9.4 v. 11.1 months, HR=1.53, 95% CI 1.12, 2.10, P=0.004) and FIRE-3 (8.8 v. 10.9 months, HR=1.40, 95% CI 1.06, 1.85, P=0.015). These associations were confirmed in multivariable analyses, and were not seen in the control cohort. In subgroup analysis, the effect of IL-6 rs2069837 on PFS was present only in patients with left-sided cancers, but the test for interaction was not significant. Conclusion IL-6 rs2069837 genotype is a clinically relevant prognostic factor in mCRC patients treated with first-line bevacizumab-based chemotherapy.

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Relationship between expression and prognostic ability of PTEN, STAT3 and VEGF-C in colorectal cancer

Cited by 32 publications

References 23 publications

Vascular Endothelial Growth Factor-C Expression as a Biomarker of Poor Prognosis in Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Vascular Endothelial Growth Factor-C Expression as a Biomarker of Poor Prognosis in Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Functions and Regulation of the PTEN Gene in Colorectal Cancer

Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy

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