The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer

Blum, Craig; Graham, Amanda S.; Yousefzadeh, M; Shrout, Jessica; Benjamin, K.; Krishna, Murli; Hoda, Raza S; Hoda, Rana S.; Cole, David J.; Garrett‐Mayer, Elizabeth; Reed, Carolyn E.; Wallace, Michael B.; Mitas, Michael

doi:10.3892/ijo_00000043

Cited by 21 publications

(20 citation statements)

References 3 publications

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“…The clinical significance of this finding is not known. However, in a subsequent study performed on untreated stage II tissues obtained from a separate institute, we discovered that low B2M expression was an independent prognostic marker for poor patient survival (Blum et al, 2008). Thus, the results described here may ultimately prove to be of benefit to a significant number of CRC patients.…”

Section: Discussionmentioning

confidence: 64%

β2microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients

et al. 2008

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Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT -PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I -IV CRC patients with (n ¼ 20) and without (n ¼ 18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of b 2 microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC) ¼ 0.85; 95% confidence interval (CI) ¼ 0.69 -0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC ¼ 0.87; 95% CI ¼ 0.71 -0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R 2 value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival.

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Section: Discussionmentioning

confidence: 64%

β2microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients

et al. 2008

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“…In support of a potential role for MAP7 in metastatic growth, this gene was recently identified as one out of only fifteen that was highly upregulated in metastatic endometrial cancer using a 22 K Affymetrix array [20]. Moreover, high MAP7 expression has been associated with tumor recurrence and poor prognosis in Stage II colon cancer patients [21]. Here, we showed that MAP7 had the potential to accelerate proliferation, but not influence apoptosis and cell cycle progression in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

The identification of novel targets of miR-16 and characterization of their biological functions in cancer cells

et al. 2013

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BackgroundIn eukaryotes, miR-16 is an important microRNA (miRNA) that is involved in numerous biological processes. However, it is not fully understood how miR-16 executes its physiological functions. In the present study, we aimed to identify novel miR-16 targets and study their biological functions.MethodsCandidate target genes of miR-16 were screened by microarray analysis of mRNA levels in several cancer cell lines with enhanced miR-16. Three bioinformatics algorithms, including TargetScan, PicTar, and miRanda, were used in combination to calculate the miR-16 targets. The expression levels of miR-16 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. The effect of miR-16 and target gene on cell viability was evaluated using MTT assays. The effects of miR-16 and target gene on apoptosis and cell cycle distribution were evaluated by flow cytometry analysis.ResultsBy overexpressing miR-16 in several cancer cell lines and measuring global mRNA levels using microarray analysis, we identified 27 genes that may be regulated by miR-16. After the bioinformatics filtering process, 18 genes were selected as candidate miR-16 targets. Furthermore, we experimentally validated three of these candidates, MAP7 (microtubule-associated protein 7), PRDM4 (PR domain containing 4) and CDS2 (CDP-diacylglycerol synthase 2), as direct targets of miR-16. Finally, we demonstrated that miR-16 targeting MAP7 played a critical role in regulating proliferation but not apoptosis and cell cycle progression in cancer cells.ConclusionIn summary, the present study identifies several novel miR-16 targets and illustrates a novel function of miR-16 targeting MAP7 in modulating proliferation in cancer cells.

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“…Menon et al 24 found that down-regulation of HLA-A corresponds to lower tumour stage, mucinous cancers, lower recurrence rates and longer disease-free survival time in 88 CRC patients. All patients with complete loss of HLA-A had no recurrence and half were MSI-H. Additionally, Blum et al 25 found that patients with tumours expressing high ratios of microtubule associate protein 7 to B2M had significantly more favourable outcome. In the FOGT-4 clinical trial Tikidzhieva et al 12 have also provided first prospective evidence that B2M mutations are associated with a trend towards absence of tumour related death events in MMR-deficient patients.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status

et al. 2012

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The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer

Cited by 21 publications

References 3 publications

β2microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients

β2microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients

The identification of novel targets of miR-16 and characterization of their biological functions in cancer cells

Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status

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