Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 7/2013

01-07-2013 | Original Paper

p42.3: A promising biomarker for the progression and prognosis of human colorectal cancer

Authors: Xiao-Sun Yuan, Yi Zhang, Xiao-Ya Guan, Bin Dong, Min Zhao, Lin-Lin Mao, You-Yong Lu, Xiu-Yun Tian, Chun-Yi Hao

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2013

Login to get access

Abstract

Purpose

As a novel cell cycle-related gene, p42.3 has been shown to play a key role in the cell proliferation and tumorigenicity of gastric cancer. To date, the association between p42.3 and colorectal cancer (CRC) has not been reported. This study investigated the expression of p42.3 and its potential role in human colorectal cancers.

Methods

Real-time polymerase chain reaction and western blotting were used to evaluate p42.3 mRNA and protein expression in 14 pairs of fresh frozen CRC samples, matched with adjacent normal mucosa. The p42.3 protein was evaluated by immunohistochemistry using CRC tissue microarrays, which included 212 CRC specimens and corresponding normal colorectal mucosa. The expression profiles of p42.3 in CRC tissues were analyzed against clinicopathological factors and post-surgical survival status. The expression profiles of p42.3 were also investigated in six human colon carcinoma cell lines.

Results

p42.3 was demonstrated to be over-expressed in colorectal cancer tissues compared with normal mucosa in the 14 tissue pairs (P = 0.011) and was significantly higher in patients with poor tumor differentiation (P = 0.045); patients positive for p42.3 expression had a poorer prognosis than those not expressing this protein (P = 0.033). In a multivariate survival analysis, p42.3 expression was identified as an independent prognostic factor for CRC patients (P = 0.030).

Conclusions

The results indicated that p42.3 might play an important role in the progression of CRC, and it has a great value for assessing CRC patient prognosis after surgery.
Literature
go back to reference Bolander A, Agnarsdottir M, Stromberg S, Ponten F, Hesselius P, Uhlen M, Bergqvist M (2008) The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas. Cancer Genomics Proteomics 5:293–300PubMed Bolander A, Agnarsdottir M, Stromberg S, Ponten F, Hesselius P, Uhlen M, Bergqvist M (2008) The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas. Cancer Genomics Proteomics 5:293–300PubMed
go back to reference Cui Y, Su WY, Xing J, Wang YC, Wang P, Chen XY, Shen ZY, Cao H, Lu YY, Fang JY (2011) MiR-29a inhibits cell proliferation and induces cell cycle arrest through the downregulation of p42.3 in human gastric cancer. PLoS ONE 6:e25872PubMedCrossRef Cui Y, Su WY, Xing J, Wang YC, Wang P, Chen XY, Shen ZY, Cao H, Lu YY, Fang JY (2011) MiR-29a inhibits cell proliferation and induces cell cycle arrest through the downregulation of p42.3 in human gastric cancer. PLoS ONE 6:e25872PubMedCrossRef
go back to reference de Vries JE, Dinjens WN, De Bruyne GK, Verspaget HW, van der Linden EP, de Bruïne AP, Mareel MM, Bosman FT, ten Kate J (1995) In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells. Br J Cancer 71:271–277PubMedCrossRef de Vries JE, Dinjens WN, De Bruyne GK, Verspaget HW, van der Linden EP, de Bruïne AP, Mareel MM, Bosman FT, ten Kate J (1995) In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells. Br J Cancer 71:271–277PubMedCrossRef
go back to reference Duranton B, Holl V, Schneider Y, Carnesecchi S, Gossé F, Raul F, Seiler N (2003) Polyamine metabolism in primary human colon adenocarcinoma cells (SW480) and their lymph node metastatic derivatives (SW620). Amino Acids 24:63–72PubMed Duranton B, Holl V, Schneider Y, Carnesecchi S, Gossé F, Raul F, Seiler N (2003) Polyamine metabolism in primary human colon adenocarcinoma cells (SW480) and their lymph node metastatic derivatives (SW620). Amino Acids 24:63–72PubMed
go back to reference Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA 104:15805–15810PubMedCrossRef Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA 104:15805–15810PubMedCrossRef
go back to reference Freemantle SJ, Liu X, Feng Q, Galimberti F, Blumen S, Sekula D, Kitareewan S, Dragnev KH, Dmitrovsky E (2007) Cyclin degradation for cancer therapy and chemoprevention. J Cell Biochem 102:869–877PubMedCrossRef Freemantle SJ, Liu X, Feng Q, Galimberti F, Blumen S, Sekula D, Kitareewan S, Dragnev KH, Dmitrovsky E (2007) Cyclin degradation for cancer therapy and chemoprevention. J Cell Biochem 102:869–877PubMedCrossRef
go back to reference Gascoigne KE, Taylor SS (2009) How do anti-mitotic drugs kill cancer cells? J Cell Sci 122:2579–2585PubMedCrossRef Gascoigne KE, Taylor SS (2009) How do anti-mitotic drugs kill cancer cells? J Cell Sci 122:2579–2585PubMedCrossRef
go back to reference Gavet O, Pines J (2010) Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell 18:533–543PubMedCrossRef Gavet O, Pines J (2010) Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell 18:533–543PubMedCrossRef
go back to reference Ghosh D, Yu H, Tan XF, Lim TK, Zubaidah RM, Tan HT, Chung MC, Lin Q (2011) Identification of key players for colorectal cancer metastasis by iTRAQ quantitative proteomics profiling of isogenic SW480 and SW620 cell lines. J Proteome Res 10:4373–4387PubMedCrossRef Ghosh D, Yu H, Tan XF, Lim TK, Zubaidah RM, Tan HT, Chung MC, Lin Q (2011) Identification of key players for colorectal cancer metastasis by iTRAQ quantitative proteomics profiling of isogenic SW480 and SW620 cell lines. J Proteome Res 10:4373–4387PubMedCrossRef
go back to reference Golan A, Pick E, Tsvetkov L, Nadler Y, Kluger H, Stern DF (2010) Centrosomal Chk2 in DNA damage responses and cell cycle progression. Cell Cycle 9:2647–2656PubMedCrossRef Golan A, Pick E, Tsvetkov L, Nadler Y, Kluger H, Stern DF (2010) Centrosomal Chk2 in DNA damage responses and cell cycle progression. Cell Cycle 9:2647–2656PubMedCrossRef
go back to reference Hamada M, Yakushijin Y, Ohtsuka M, Kakimoto M, Yasukawa M, Fujita S (2003) Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-hodgkin’s lymphoma. Br J Haematol 121:439–447PubMedCrossRef Hamada M, Yakushijin Y, Ohtsuka M, Kakimoto M, Yasukawa M, Fujita S (2003) Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-hodgkin’s lymphoma. Br J Haematol 121:439–447PubMedCrossRef
go back to reference Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM (2004) VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 10:262–267PubMedCrossRef Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM (2004) VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 10:262–267PubMedCrossRef
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef
go back to reference Jung Y, Lee S, Choi HS, Kim SN, Lee E, Shin Y, Seo J, Kim B, Jung Y, Kim WK, Chun HK, Lee WY, Kim J (2011) Clinical validation of colorectal cancer biomarkers identified from bioinformatics analysis of public expression data. Clin Cancer Res 17:700–709PubMedCrossRef Jung Y, Lee S, Choi HS, Kim SN, Lee E, Shin Y, Seo J, Kim B, Jung Y, Kim WK, Chun HK, Lee WY, Kim J (2011) Clinical validation of colorectal cancer biomarkers identified from bioinformatics analysis of public expression data. Clin Cancer Res 17:700–709PubMedCrossRef
go back to reference Kelling J, Sullivan K, Wilson L, Jordan MA (2003) Suppression of centromere dynamics by taxol in living osteosarcoma cells. Cancer Res 63:2794–2801PubMed Kelling J, Sullivan K, Wilson L, Jordan MA (2003) Suppression of centromere dynamics by taxol in living osteosarcoma cells. Cancer Res 63:2794–2801PubMed
go back to reference Leibovitz A, Stinson JC, McCombs WB 3rd, McCoy CE, Mazur KC, Mabry ND (1976) Classification of human colorectal adenocarcinoma cell lines. Cancer Res 36:4562–4569PubMed Leibovitz A, Stinson JC, McCombs WB 3rd, McCoy CE, Mazur KC, Mabry ND (1976) Classification of human colorectal adenocarcinoma cell lines. Cancer Res 36:4562–4569PubMed
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408PubMedCrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408PubMedCrossRef
go back to reference Lyall MS, Dundas SR, Curran S, Murray GI (2006) Profiling markers of prognosis in colorectal cancer. Clin Cancer Res 12:1184–1191PubMedCrossRef Lyall MS, Dundas SR, Curran S, Murray GI (2006) Profiling markers of prognosis in colorectal cancer. Clin Cancer Res 12:1184–1191PubMedCrossRef
go back to reference Mao L, Sun W, Li W, Cui J, Zhang J, Xing R, Lu Y (2012) Cell cycle-dependent expression of p42.3 promotes mitotic progression in malignant transformed cells. Mol Carcinog. doi:10.1002/mc.21982 Mao L, Sun W, Li W, Cui J, Zhang J, Xing R, Lu Y (2012) Cell cycle-dependent expression of p42.3 promotes mitotic progression in malignant transformed cells. Mol Carcinog. doi:10.​1002/​mc.​21982
go back to reference Mott JL, Kobayashi S, Bronk SF, Gores GJ (2007) mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26:6133–6140PubMedCrossRef Mott JL, Kobayashi S, Bronk SF, Gores GJ (2007) mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26:6133–6140PubMedCrossRef
go back to reference Muniyappa MK, Dowling P, Henry M, Meleady P, Doolan P, Gammell P, Clynes M, Barron N (2009) MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. Eur J Cancer 45:3104–3118PubMedCrossRef Muniyappa MK, Dowling P, Henry M, Meleady P, Doolan P, Gammell P, Clynes M, Barron N (2009) MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. Eur J Cancer 45:3104–3118PubMedCrossRef
go back to reference Okouneva T, Hill BT, Wilson L, Jordan MA (2003) The effects of vinflunine, vinorelbine, and vinblastine on centromere dynamics. Mol Cancer Ther 2:427–436PubMed Okouneva T, Hill BT, Wilson L, Jordan MA (2003) The effects of vinflunine, vinorelbine, and vinblastine on centromere dynamics. Mol Cancer Ther 2:427–436PubMed
go back to reference Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, Croce CM (2006) Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66:11590–11593PubMedCrossRef Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, Croce CM (2006) Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66:11590–11593PubMedCrossRef
go back to reference Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed
go back to reference Schwartz GK, Shah MA (2005) Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol 23:9408–9421PubMedCrossRef Schwartz GK, Shah MA (2005) Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol 23:9408–9421PubMedCrossRef
go back to reference Stone A, Sutherland RL, Musgrove EA (2012) Inhibitors of cell cycle kinases: recent advances and future prospects as cancer therapeutics. Crit Rev Oncog 17:175–198PubMedCrossRef Stone A, Sutherland RL, Musgrove EA (2012) Inhibitors of cell cycle kinases: recent advances and future prospects as cancer therapeutics. Crit Rev Oncog 17:175–198PubMedCrossRef
go back to reference Takahashi T, Sano B, Nagata T, Kato H, Sugiyama Y, Kunieda K, Kimura M, Okano Y, Saji S (2003) Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers. Cancer Sci 94:148–152PubMedCrossRef Takahashi T, Sano B, Nagata T, Kato H, Sugiyama Y, Kunieda K, Kimura M, Okano Y, Saji S (2003) Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers. Cancer Sci 94:148–152PubMedCrossRef
go back to reference Vankayalapati H, Bearss DJ, Saldanha JW, Muñoz RM, Rojanala S, Von Hoff DD, Mahadevan D (2003) Targeting aurora2 kinase in oncogenesis: a structural bioinformatics approach to target validation and rational drug design. Mol Cancer Ther 2:283–294PubMed Vankayalapati H, Bearss DJ, Saldanha JW, Muñoz RM, Rojanala S, Von Hoff DD, Mahadevan D (2003) Targeting aurora2 kinase in oncogenesis: a structural bioinformatics approach to target validation and rational drug design. Mol Cancer Ther 2:283–294PubMed
go back to reference Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC (2008) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14:369–381PubMedCrossRef Wang H, Garzon R, Sun H, Ladner KJ, Singh R, Dahlman J, Cheng A, Hall BM, Qualman SJ, Chandler DS, Croce CM, Guttridge DC (2008) NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. Cancer Cell 14:369–381PubMedCrossRef
go back to reference Xu F, Wang F, Di M, Huang Q, Wang M, Hu H, Jin Y, Dong J, Lai M (2007a) Classification based on the combination of molecular and pathologic predictors is superior to molecular classification on prognosis in colorectal carcinoma. Clin Cancer Res 13:5082–5088PubMedCrossRef Xu F, Wang F, Di M, Huang Q, Wang M, Hu H, Jin Y, Dong J, Lai M (2007a) Classification based on the combination of molecular and pathologic predictors is superior to molecular classification on prognosis in colorectal carcinoma. Clin Cancer Res 13:5082–5088PubMedCrossRef
go back to reference Xu X, Li W, Fan X, Liang Y, Zhao M, Zhang J, Liang Y, Tong W, Wang J, Yang W, Lu Y (2007b) Identification and characterization of a novel p42.3 gene as tumor-specific and mitosis phase-dependent expression in gastric cancer. Oncogene 26:7371–7379PubMedCrossRef Xu X, Li W, Fan X, Liang Y, Zhao M, Zhang J, Liang Y, Tong W, Wang J, Yang W, Lu Y (2007b) Identification and characterization of a novel p42.3 gene as tumor-specific and mitosis phase-dependent expression in gastric cancer. Oncogene 26:7371–7379PubMedCrossRef
go back to reference Zeng JZ, Wang HY, Chen ZJ, Ullrich A, Wu MC (2002) Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma. Oncogene 21:4932–4943PubMedCrossRef Zeng JZ, Wang HY, Chen ZJ, Ullrich A, Wu MC (2002) Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma. Oncogene 21:4932–4943PubMedCrossRef
go back to reference Zhang J, Lu C, Shang Z, Xing R, Shi L, Lv Y (2012a) p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis. Theor Biol Med Model 9:53PubMedCrossRef Zhang J, Lu C, Shang Z, Xing R, Shi L, Lv Y (2012a) p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis. Theor Biol Med Model 9:53PubMedCrossRef
go back to reference Zhang Y, Guan XY, Dong B, Zhao M, Wu JH, Tian XY, Hao CY (2012b) Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features. J Cancer Res Clin Oncol 138:2035–2044PubMedCrossRef Zhang Y, Guan XY, Dong B, Zhao M, Wu JH, Tian XY, Hao CY (2012b) Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features. J Cancer Res Clin Oncol 138:2035–2044PubMedCrossRef
Metadata
Title
p42.3: A promising biomarker for the progression and prognosis of human colorectal cancer
Authors
Xiao-Sun Yuan
Yi Zhang
Xiao-Ya Guan
Bin Dong
Min Zhao
Lin-Lin Mao
You-Yong Lu
Xiu-Yun Tian
Chun-Yi Hao
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 7/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-013-1434-0

Other articles of this Issue 7/2013

Journal of Cancer Research and Clinical Oncology 7/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.