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Alternative polyadenylation is associated with lower expression of PABPN1 and poor prognosis in non-small cell lung cancer.

Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, Yatomi Y, Ohishi N, Takai D - Cancer Sci. (2014)

Bottom Line: We selected the top 10 genes showing significant 3'UTR shortening in lung cancer, using the package of the Bioconductor for probe-level analyses of expression microarrays.We established and evaluated the APA score by quantitative RT-PCR in 147 clinical specimens of non-small cell lung cancer and compared the results with the clinical outcomes and expression levels of APA-related genes, including PABPN1, CPEB1, E2F1 and proliferation markers (MKI67, TOP2A and MCM2).Moreover, the APA score was correlated with the maximum standardized uptake value of the tumors on positron emission tomography (r = 0.53; P < 0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, University of Tokyo Hospital, Tokyo, Japan.

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Identification of the alternative polyadenylation (APA)-indicator genes in non-small cell lung cancer. (a) The APA status of the 16 genes selected in silico was confirmed in seven clinical lung cancer specimens and eight normal lung tissue specimens, and the top 10 genes were selected as the APA-indicator genes. The APA status was evaluated on the basis of the logarithm of the proportion of the full-length transcripts of the lung cancer specimens normalized to that of the normal lung tissue specimens. Results are shown as the average ± SD. The columns over the red line indicate that the proportion of the full-length transcripts of the lung cancer specimens is less than half of that of the normal lung tissue specimens. (b) The genes selected based on the results of past studies were associated with a lower frequency of 3′UTR shortening as compared to the APA-indicator genes.
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fig03: Identification of the alternative polyadenylation (APA)-indicator genes in non-small cell lung cancer. (a) The APA status of the 16 genes selected in silico was confirmed in seven clinical lung cancer specimens and eight normal lung tissue specimens, and the top 10 genes were selected as the APA-indicator genes. The APA status was evaluated on the basis of the logarithm of the proportion of the full-length transcripts of the lung cancer specimens normalized to that of the normal lung tissue specimens. Results are shown as the average ± SD. The columns over the red line indicate that the proportion of the full-length transcripts of the lung cancer specimens is less than half of that of the normal lung tissue specimens. (b) The genes selected based on the results of past studies were associated with a lower frequency of 3′UTR shortening as compared to the APA-indicator genes.

Mentions: Using the rmodel, we selected 16 genes that showed 3′UTR shortening in more than 20 of the 40 lung adenocarcinoma specimens included within the GSE10245 dataset (Table S3). All 16 genes showed 3′UTR shortening in more than 10 of the 18 lung squamous cell carcinoma specimens within the GSE10245 dataset (Table S3). The APA status of the 16 genes was confirmed in 7 clinical lung cancer specimens and 8 normal lung tissue specimens (Fig.3), and the top 10 genes which showed more marked APA in lung cancer were selected as the APA-indicator genes (C1orf52, DIEXF, ESYT2, HN1L, MUC20, NDFIP2, RBM33, SCAMP1, SMC1A and SSR1). For subsequent analysis, we defined the APA score as the total number of genes that showed 3′UTR shortening among the 10 APA-indicator genes.


Alternative polyadenylation is associated with lower expression of PABPN1 and poor prognosis in non-small cell lung cancer.

Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, Yatomi Y, Ohishi N, Takai D - Cancer Sci. (2014)

Identification of the alternative polyadenylation (APA)-indicator genes in non-small cell lung cancer. (a) The APA status of the 16 genes selected in silico was confirmed in seven clinical lung cancer specimens and eight normal lung tissue specimens, and the top 10 genes were selected as the APA-indicator genes. The APA status was evaluated on the basis of the logarithm of the proportion of the full-length transcripts of the lung cancer specimens normalized to that of the normal lung tissue specimens. Results are shown as the average ± SD. The columns over the red line indicate that the proportion of the full-length transcripts of the lung cancer specimens is less than half of that of the normal lung tissue specimens. (b) The genes selected based on the results of past studies were associated with a lower frequency of 3′UTR shortening as compared to the APA-indicator genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4462401&req=5

fig03: Identification of the alternative polyadenylation (APA)-indicator genes in non-small cell lung cancer. (a) The APA status of the 16 genes selected in silico was confirmed in seven clinical lung cancer specimens and eight normal lung tissue specimens, and the top 10 genes were selected as the APA-indicator genes. The APA status was evaluated on the basis of the logarithm of the proportion of the full-length transcripts of the lung cancer specimens normalized to that of the normal lung tissue specimens. Results are shown as the average ± SD. The columns over the red line indicate that the proportion of the full-length transcripts of the lung cancer specimens is less than half of that of the normal lung tissue specimens. (b) The genes selected based on the results of past studies were associated with a lower frequency of 3′UTR shortening as compared to the APA-indicator genes.
Mentions: Using the rmodel, we selected 16 genes that showed 3′UTR shortening in more than 20 of the 40 lung adenocarcinoma specimens included within the GSE10245 dataset (Table S3). All 16 genes showed 3′UTR shortening in more than 10 of the 18 lung squamous cell carcinoma specimens within the GSE10245 dataset (Table S3). The APA status of the 16 genes was confirmed in 7 clinical lung cancer specimens and 8 normal lung tissue specimens (Fig.3), and the top 10 genes which showed more marked APA in lung cancer were selected as the APA-indicator genes (C1orf52, DIEXF, ESYT2, HN1L, MUC20, NDFIP2, RBM33, SCAMP1, SMC1A and SSR1). For subsequent analysis, we defined the APA score as the total number of genes that showed 3′UTR shortening among the 10 APA-indicator genes.

Bottom Line: We selected the top 10 genes showing significant 3'UTR shortening in lung cancer, using the package of the Bioconductor for probe-level analyses of expression microarrays.We established and evaluated the APA score by quantitative RT-PCR in 147 clinical specimens of non-small cell lung cancer and compared the results with the clinical outcomes and expression levels of APA-related genes, including PABPN1, CPEB1, E2F1 and proliferation markers (MKI67, TOP2A and MCM2).Moreover, the APA score was correlated with the maximum standardized uptake value of the tumors on positron emission tomography (r = 0.53; P < 0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, University of Tokyo Hospital, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus