Identification of novel molecular markers for detection of gastric cancer cells in the peripheral blood circulation using genome-wide microarray analysis

Matsumura, Nobuyuki; Zembutsu, Hitoshi; Yamaguchi, Koji; Sasaki, Kohsuke; Tsuruma, Tetsuhiro; Nishidate, Toshihiko; Denno, Ryuichi; Hirata, Koichi

doi:10.3892/etm.2011.252

Cited by 24 publications

(24 citation statements)

References 33 publications

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“…Although the overexpression of tetraspanin 8 has been described in relation to several human cancers [10][11][12][13], and it has been also reported that TSPAN8 mRNA is upregulated in the GC tissues compared to the normal gastric tissues by microarray analysis [14], the significance of tetraspanin 8 protein in GC remains unclear. Immunohistochemical analysis revealed that tetraspanin 8 protein was expressed in GC cells and that 72 (34 %) of 210 GC cases were positive for tetraspanin 8.…”

Section: Discussionmentioning

confidence: 99%

“…Tetraspanins are involved in adhesion, motility, matrix modulation, and cell fusion [9]. Although it has been reported that TSPAN8 is expressed in the GC cell line [24], and that TSPAN8 mRNA is upregulated in GC tissues compared to normal gastric tissues according to microarray analysis [14], detailed expression of TSPAN8 has not been investigated. Among the 14 types of normal tissue, low-level TSPAN8 mRNA expression was detected in normal small intestine, colon, and liver.…”

Section: Generation Of the Mkn-45 Cast Librarymentioning

confidence: 99%

“…In human cancers, overexpression of tetraspanin 8 has been reported in relation to hepatocellular carcinoma [10], pancreatic cancer [11], colon cancer [12], and esophageal cancer [13]. It has been also reported that TSPAN8 mRNA is upregulated in the GC tissues compared to normal gastric tissues by microarray analysis [14]. Furthermore, tetraspanins have been reported to be components of exosomes [15], and exosomes containing rat TSPAN8 have been shown to affect tumor cell migration, proliferation, and tumor angiogenesis [16].…”

Section: Introductionmentioning

confidence: 99%

“…TSPAN8 encodes tetraspanin 8 protein, which is a member of the tetraspanin family. It has been reported that TSPAN8 is highly expressed in several types of human cancer [10][11][12][13][14]. Tetraspanins are involved in adhesion, motility, matrix modulation, and cell fusion [9].…”

Section: Generation Of the Mkn-45 Cast Librarymentioning

confidence: 99%

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TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

et al. 2015

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Background Gastric cancer (GC) is one of the most common human cancers. Genes expressed only in cancer tissue, especially on the cell membrane, will be useful biomarkers for cancer diagnosis and therapeutics. Methods To identify novel genes encoding transmembrane protein specifically expressed in GC, we generated an Escherichia coli ampicillin secretion trap (CAST) library from diffuse-type GC cell line MKN-45. CAST is a survival-based signal sequence trap method that exploits the ability of mammalian signal sequences to confer ampicillin resistance to a mutant b-lactamase lacking the endogenous signal sequence. Results By sequencing 1,536 colonies, we identified 23 genes encoding the transmembrane protein present in GC. Among these genes, TSPAN8 (also known as CO-029 and TM4SF3) gene, which encodes transmembrane protein tetraspanin 8, was emphasized as a candidate. Immunohistochemical analysis of tetraspanin 8 in human GC tissues revealed that 72 (34 %) of 210 GC cases were positive for tetraspanin 8, and microvessel density was significantly higher in tetraspanin 8-positive GC than in tetraspanin 8-negative GC. Furthermore, univariate and multivariate analyses revealed that tetraspanin 8 expression is an independent prognostic classifier of patients with GC. TSPAN8 knockdown by siRNA reduced the invasion of GC cell line. The reduction of invasiveness was retrieved by the tetraspanin 8-containing exosome. Conclusion These results suggest that tetraspanin 8 is involved in tumor progression and is an independent prognostic classifier in patients with GC.

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Section: Discussionmentioning

confidence: 99%

Section: Generation Of the Mkn-45 Cast Librarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Generation Of the Mkn-45 Cast Librarymentioning

confidence: 99%

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TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

et al. 2015

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“…High-throughput cancer cell line screening provides a strategy to identify transcription markers to help guide targeted cancer therapy (38,39). Here, we present a computational strategy to profile unique transcriptional signatures associated with somatic mutations in combination with cancer lineage, using two metrics reflecting sensitivity and specificity independently.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Transcriptomes of Cancer Cell Lines and Patient Samples Reveals STK11/LKB1–Driven Regulation of cAMP Phosphodiesterase-4D

Kim

Song

et al. 2014

Molecular Cancer Therapeutics

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The recent proliferation of data on large collections of well-characterized cancer cell lines linked to therapeutic drug responses has made it possible to identify lineage-and mutation-specific transcriptional markers that can help optimize implementation of anticancer agents. Here, we leverage these resources to systematically investigate the presence of mutation-specific transcription markers in a wide variety of cancer lineages and genotypes. Sensitivity and specificity of potential transcriptional biomarkers were simultaneously analyzed in 19 cell lineages grouped into 228 categories based on the mutational genotypes of 12 cancer-related genes. Among a total of 1,455 category-specific expression patterns, the expression of cAMP phosphodiesterase-4D (PDE4D) with 11 isoforms, one of the PDE4(A-D) subfamilies, was predicted to be regulated by a mutant form of serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) present in lung cancer. STK11/ LKB1 is the primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK). Subsequently, we found that the knockdown of PDE4D gene expression inhibited proliferation of STK11-mutated lung cancer lines. Furthermore, challenge with a panel of PDE4-specific inhibitors was shown to selectively reduce the growth of STK11-mutated lung cancer lines. Thus, we show that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets. Mol Cancer Ther; 13(10); 2463-73. Ó2014 AACR.

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KIAA0101 mRNA overexpression in peripheral blood mononuclear cells acts as predictive marker for hepatic cancer

Zhang

Peng

et al. 2013

Tumor Biol.

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KIAA0101 always overexpresses in tumor tissues, which is also a marker of tumor recurrence. This study aims to explore whether overexpression of KIAA0101 mRNA in peripheral blood mononuclear cells (PBMCs) could act as a noninvasive and predictive biomarker of hepatic cancer. Real-time polymerase chain reaction (RT-PCR) was employed to detect KIAA0101 mRNA expression in PBMCs isolated from 93 hepatic cancer patients and 55 healthy individuals. The diagnostic sensitivity and specificity of KIAA0101 mRNA, CEA, and CD44V were analyzed and compared. A multivariate logistic regression analysis was utilized to analyze risk factors for overall survival of hepatic cancer patients. A concordance analysis was employed to compare the overexpression of KIAA0101 mRNA with clinicopathological diagnosis. All of the 93 hepatic cancer patients were followed up routinely at least 36 months or until death to analyze the 3-year overall survival rate. The results indicated that KIAA0101 mRNA expression was increased significantly in hepatic patients' PBMCs, when compared with that of healthy individuals (P < 0.05). Both the sensitivity and specificity of KIAA0101 mRNA in PBMCs were enhanced significantly compared with those of the CEA and CD44V biomarkers. The multivariate logistic regression analysis indicated that the KIAA0101 mRNA level and pTNM stage were significantly related with the overall survival of the hepatic patients. There was a better concordance between KIAA0101 mRNA overexpression and clinicopathological diagnosis for hepatic cancer (kappa = 0.914, P < 0.001). KIAA0101 mRNA overexpression in PBMCs decreased the 3-year survival rate significantly. In conclusion, overexpression of KIAA0101 mRNA in PBMCs could act as a predictive biomarker for hepatic cancer and has a better sensitivity and specificity.

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Identification of novel molecular markers for detection of gastric cancer cells in the peripheral blood circulation using genome-wide microarray analysis

Cited by 24 publications

References 33 publications

TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer

Integrated Analysis of Transcriptomes of Cancer Cell Lines and Patient Samples Reveals STK11/LKB1–Driven Regulation of cAMP Phosphodiesterase-4D

KIAA0101 mRNA overexpression in peripheral blood mononuclear cells acts as predictive marker for hepatic cancer

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