Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

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.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2014

Open Access 01-12-2014 | Research

Levels of HOXB7 and miR-337 in pancreatic ductal adenocarcinoma patients

Authors: Rui Zhang, Shangen Zheng, Yuwen Du, Yuanyuan Wang, Wenqiao Zang, Guoqiang Zhao

Published in: Diagnostic Pathology | Issue 1/2014

Login to get access

Abstract

Background

Many studies have revealed that homeobox-B7 (HOXB7) and miR-337 play important roles in different types of human cancers. However, the relationship of HOXB7 and miR-337 in PDAC with clinicopathological factors has not yet been examined and their biological roles remain to be explored.

Methods

Using quantitative real-time RT-PCR and immunohistochemical staining, the expression of HOXB7 mRNA, miR-337, and HOXB7 protein in 44 PDAC samples was detected. Survival curves were made using follow-up data. The relationship between clinical or pathological characteristics and the prognosis was analyzed.

Results

The expression levels of HOXB7 mRNA and HOXB7 protein were significantly elevated in PDAC samples than that in non-malignant adjacent tissues. There were obvious differences in HOXB7 mRNA and proteins between tumors of different diameters, differentiation, TNM stage, and lymph node status. The level of miR-337 was markedly lower in tumor samples than in non-malignant adjacent tissues. The expression of miR-337 was related to TNM stage and lymph node status. There were significant differences in survival curves between patients with tumors <4 cm in diameter and patients with tumors ≥4 cm, among groups of well, moderately, and poorly differentiated tumors, between groups with TNM stages I, II and III or IV, between groups with metastatic lymph nodes and non-metastatic lymph nodes, among groups of HOXB7 protein expression negative (or weak) and positive, between groups with low levels of miR-337 expression and with high levels of miR-337 expression. The levels of HOXB7 mRNA, HOXB7 protein, and miR-337 were found to be associated with longer survival.

Conclusion

The present study showed that HOXB7 was over-expressed and miR-337 was minimally expressed in PDAC tissues, and their levels were related to TNM stage and lymph node status. The levels of HOXB7 mRNA, HOXB7 protein, and miR-337 were associated with survival in PDAC patients. Results suggested that HOXB7 and miR-337 could be used as determinants of PDAC patient prognosis.

Virtual slides

The virtual slides for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1509730773118658​.
Appendix
Available only for authorised users
Literature
1.
Herreros-Villanueva M, Hijona E, Cosme A, Bujanda L: Adjuvant and neoadjuvant treatment in pancreatic cancer. World J Gastroenterol. 2012, 18 (14): 1565-1572. 10.3748/wjg.v18.i14.1565.PubMedPubMedCentralCrossRef
2.
Páez D, Labonte MJ, Lenz HJ: Pancreatic cancer: medical management (novel chemotherapeutics). Gastroenterol Clin North Am. 2012, 41 (1): 189-209. 10.1016/j.gtc.2011.12.004.PubMedCrossRef
3.
Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR: The pathophysiology of HOX genes and their role in cancer. J Pathol. 2005, 205 (2): 154-171. 10.1002/path.1710.PubMedCrossRef
4.
Nunes FD, de Almeida FC, Tucci R, de Sousa SC: Homeobox genes: a molecular link between development and cancer. Pesqui Odontol Bras. 2003, 17 (1): 94-98. 10.1590/S1517-74912003000100018.PubMedCrossRef
5.
6.
Gray S, Pandha HS, Michael A, Middleton G, Morgan R: HOX genes in pancreatic development and cancer. JOP. 2011, 12 (3): 216-219.PubMed
7.
Cantile M, Scognamiglio G, La Sala L, La Mantia E, Scaramuzza V, Valentino E, Tatangelo F, Losito S, Pezzullo L, Chiofalo MG, Fulciniti F, Franco R, Botti G: Aberrant expression of posterior HOX genes in well differentiated histotypes of thyroid cancers. Int J Mol Sci. 2013, 14 (11): 21727-21740. 10.3390/ijms141121727.PubMedPubMedCentralCrossRef
8.
Kanai M, Hamada J, Takada M, Asano T, Murakawa K, Takahashi Y, Murai T, Tada M, Miyamoto M, Kondo S, Moriuchi T: Aberrant expressions of HOX genes in colorectal and hepatocellular carcinomas. Oncol Rep. 2010, 23 (3): 843-851.PubMed
9.
Shimoda M, Takahashi M, Yoshimoto T, Kono T, Ikai I, Kubo H: A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma. Clin Cancer Res. 2006, 12 (20 Pt 1): 6005-6011.PubMedCrossRef
10.
Hong JH, Lee JK, Park JJ, Lee NW, Lee KW, Na JY: Expression pattern of the class I homeobox genes in ovarian carcinoma. J Gynecol Oncol. 2010, 21 (1): 29-37. 10.3802/jgo.2010.21.1.29.PubMedPubMedCentralCrossRef
11.
Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco M, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S: HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci USA. 2010, 107 (3): 1100-1105. 10.1073/pnas.0912710107.PubMedPubMedCentralCrossRef
12.
Petrini M, Felicetti F, Bottero L, Errico MC, Morsilli O, Boe A, De Feo A, Carè A: HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line. Cancer Cell Int. 2013, 13 (1): 101-10.1186/1475-2867-13-101.PubMedPubMedCentralCrossRef
13.
Nischalke HD, Schmitz V, Luda C, Aldenhoff K, Berger C, Feldmann G, Sauerbruch T, Spengler U, Nattermann J: Detection of IGF2BP3, HOXB7, and NEK2 mRNA expression in brush cytology specimens as a new diagnostic tool in patients with biliary strictures. PLoS One. 2012, 7 (8): e42141-10.1371/journal.pone.0042141.PubMedPubMedCentralCrossRef
14.
di Pietro M, Lao-Sirieix P, Boyle S, Cassidy A, Castillo D, Saadi A, Eskeland R, Fitzgerald RC: Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus. Proc Natl Acad Sci USA. 2012, 109 (23): 9077-9082. 10.1073/pnas.1116933109.PubMedPubMedCentralCrossRef
15.
Jin K, Kong X, Shah T, Penet MF, Wildes F, Sgroi DC, Ma XJ, Huang Y, Kallioniemi A, Landberg G, Bieche I, Wu X, Lobie PE, Davidson NE, Bhujwalla ZM, Zhu T, Sukumar S: The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. Proc Natl Acad Sci USA. 2012, 109 (8): 2736-2741. 10.1073/pnas.1018859108.PubMedPubMedCentralCrossRef
16.
Storti P, Donofrio G, Colla S, Airoldi I, Bolzoni M, Agnelli L, Abeltino M, Todoerti K, Lazzaretti M, Mancini C, Ribatti D, Bonomini S, Franceschi V, Pistoia V, Lisignoli G, Pedrazzini A, Cavicchi O, Neri A, Rizzoli V, Giuliani N: HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients. Leukemia. 2011, 25 (3): 527-537. 10.1038/leu.2010.270.PubMedCrossRef
17.
Yamashita T, Tazawa S, Yawei Z, Katayama H, Kato Y, Nishiwaki K, Yokohama Y, Ishikawa M: Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells. Int J Oncol. 2006, 28 (4): 931-938.PubMed
18.
Wu X, Chen H, Parker B, Rubin E, Zhu T, Lee JS, Argani P, Sukumar S: HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. Cancer Res. 2006, 66 (19): 9527-9534. 10.1158/0008-5472.CAN-05-4470.PubMedCrossRef
19.
Zamore PD, Haley B: Ribo-gnome: the big world of small RNAs. Science. 2005, 309 (5740): 1519-1524. 10.1126/science.1111444.PubMedCrossRef
20.
21.
Zhu M, Xu Z, Wang K, Wang N, Li Y: microRNA and gene networks in human pancreatic cancer. Oncol Lett. 2013, 6 (4): 1133-1139.PubMedPubMedCentral
22.
Deng J, He M, Chen L, Chen C, Zheng J, Cai Z: The loss of miR-26a-mediated post-transcriptional regulation of cyclin E2 in pancreatic cancer cell proliferation and decreased patient survival. PLoS One. 2013, 8 (10): e76450-10.1371/journal.pone.0076450.PubMedPubMedCentralCrossRef
23.
Zhao G, Wang B, Liu Y, Zhang JG, Deng SC, Qin Q, Tian K, Li X, Zhu S, Niu Y, Gong Q, Wang CY: miRNA-141, downregulated in pancreatic cancer, inhibits cell proliferation and invasion by directly targeting MAP4K4. Mol Cancer Ther. 2013, 12 (11): 2569-2580. 10.1158/1535-7163.MCT-13-0296.PubMedCrossRef
24.
Cheng H, Shi S, Cai X, Long J, Xu J, Liu C, Yu X: microRNA signature for human pancreatic cancer invasion and metastasis. Exp Ther Med. 2012, 4 (2): 181-187.PubMedPubMedCentral
25.
Plummer PN, Freeman R, Taft RJ, Vider J, Sax M, Umer BA, Gao D, Johns C, Mattick JS, Wilton SD, Ferro V, McMillan NA, Swarbrick A, Mittal V, Mellick AS: MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. Cancer Res. 2013, 73 (1): 341-352. 10.1158/0008-5472.CAN-12-0271.PubMedCrossRef
26.
Palmieri A, Pezzetti F, Brunelli G, Martinelli M, Scapoli L, Arlotti M, Masiero E, Carinci F: Medpor regulates osteoblast’s microRNAs. Biomed Mater Eng. 2008, 18 (2): 91-97.PubMed
27.
Palmieri A, Pezzetti F, Spinelli G, Arlotti M, Avantaggiato A, Scarano A, Scapoli L, Zollino I, Carinci F: PerioGlas regulates osteoblast RNA interfering. J Prosthodont. 2008, 17 (7): 522-526. 10.1111/j.1532-849X.2008.00331.x.PubMedCrossRef
28.
Annalisa P, Furio P, Ilaria Z, Anna A, Luca S, Marcella M, Marzia A, Elena M, Carinci F: Anorganic bovine bone and a silicate-based synthetic bone activate different microRNAs. J Oral Sci. 2008, 50 (3): 301-307. 10.2334/josnusd.50.301.PubMedCrossRef
29.
Li Y, Zhang M, Chen H, Dong Z, Ganapathy V, Thangaraju M, Huang S: Ratio of miR-196 s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. Cancer Res. 2010, 70 (20): 7894-7904. 10.1158/0008-5472.CAN-10-1675.PubMedPubMedCentralCrossRef
30.
Zhong N, Sun J, Min Z, Zhao W, Zhang R, Wang W, Tian J, Tian L, Ma J, Li D, Han Y, Lu S: MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression. Osteoarthritis Cartilage. 2012, 20 (6): 593-602. 10.1016/j.joca.2012.03.002.PubMedCrossRef
31.
Surlin V, Ramboiu S, Ghilusi M, Plesea IE: Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis. Diagn Pathol. 2012, 7: 132-10.1186/1746-1596-7-132.PubMedPubMedCentralCrossRef
32.
Wang T, Liang YM, Hu P, Cheng YF: Mucins differently expressed in various ampullary adenocarcinomas. Diagn Pathol. 2011, 6: 102-10.1186/1746-1596-6-102.PubMedPubMedCentralCrossRef
33.
De Souza Setubal Destro MF, Bitu CC, Zecchin KG, Graner E, Lopes MA, Kowalski LP, Coletta RD: Overexpression of HOXB7 homeobox gene in oral cancer induces cellular proliferation and is associated with poor prognosis. Int J Oncol. 2010, 36 (1): 141-149.PubMed
34.
Chen H, Lee JS, Liang X, Zhang H, Zhu T, Zhang Z, Taylor ME, Zahnow C, Feigenbaum L, Rein A, Sukumar S: Hoxb7 inhibits transgenic HER-2/ neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. Cancer Res. 2008, 68 (10): 3637-3644. 10.1158/0008-5472.CAN-07-2926.PubMedPubMedCentralCrossRef
35.
Yuan W, Zhang X, Xu Y, Li S, Hu Y, Wu S: Role of HOXB7 in regulation of progression and metastasis of human lung adenocarcinoma. Mol Carcinog. 2014, 53 (1): 49-57. 10.1002/mc.21947.PubMedCrossRef
36.
Xie X, Zhang SS, Wen J, Yang H, Luo KJ, Yang F, Hu Y, Fu JH: Prognostic value of HOXB7 mRNA expression in human oesophageal squamous cell cancer. Biomarkers. 2013, 18 (4): 297-303. 10.3109/1354750X.2013.773380.PubMedCrossRef
37.
Liao WT, Jiang D, Yuan J, Cui YM, Shi XW, Chen CM, Bian XW, Deng YJ, Ding YQ: HOXB7 as a prognostic factor and mediator of colorectal cancer progression. Clin Cancer Res. 2011, 17 (11): 3569-3578. 10.1158/1078-0432.CCR-10-2533.PubMedCrossRef
38.
Nguyen Kovochich A, Arensman M, Lay AR, Rao NP, Donahue T, Li X, French SW, Dawson DW: HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma. Cancer. 2013, 119 (3): 529-539. 10.1002/cncr.27725.PubMedCrossRef
39.
Chile T, Fortes MA, Corrêa-Giannella ML, Brentani HP, Maria DA, Puga RD, de Paula Vde J, Kubrusly MS, Novak EM, Bacchella T, Giorgi RR: HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis. BMC Cancer. 2013, 13: 451-10.1186/1471-2407-13-451.PubMedPubMedCentralCrossRef
40.
How C, Hui AB, Alajez NM, Shi W, Boutros PC, Clarke BA, Yan R, Pintilie M, Fyles A, Hedley DW, Hill RP, Milosevic M, Liu FF: MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. PLoS One. 2013, 8 (7): e67846-10.1371/journal.pone.0067846.PubMedPubMedCentralCrossRef
Metadata
Title
Levels of HOXB7 and miR-337 in pancreatic ductal adenocarcinoma patients
Authors
Rui Zhang
Shangen Zheng
Yuwen Du
Yuanyuan Wang
Wenqiao Zang
Guoqiang Zhao
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2014
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-9-61

Other articles of this Issue 1/2014

Diagnostic Pathology 1/2014 Go to the issue

Editorial

Diagnostic pathology in 2013: facts, thoughts, and perspectives

Research

Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma

Case Report

Does prostate acinar adenocarcinoma with Gleason Score 3 + 3 = 6 have the potential to metastasize?

Research

Prognostic value of miR-96 in patients with acute myeloid leukemia

Research

Activation of P21-activated protein kinase 2 is an independent prognostic predictor for patients with gastric cancer

Case Report

Low-grade myxofibrosarcoma following a metal implantation in femur: a case report