Preoperative heat shock protein 47&nbsp;levels identify colorectal cancer patients with lymph node metastasis and poor prognosis

Mori,Koichiro; Toiyama,Yuji; Okugawa,Yoshinaga; Ichikawa,Takashi; Nagano,Yuka; Oki,Satoshi; Shimura,Tadanobu; Fujikawa,Hiroyuki; Hiro,Junichiro; Kobayash,Minako; Araki,Toshimitsu; Inoue,Yasuhiro; Mohri,Yasuhiko; Kusunoki,Masato

doi:10.3892/ol.2020.12196

Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis

Authors:
- Koichiro Mori
- Yuji Toiyama
- Yoshinaga Okugawa
- Takashi Ichikawa
- Yuka Nagano
- Satoshi Oki
- Tadanobu Shimura
- Hiroyuki Fujikawa
- Junichiro Hiro
- Minako Kobayash
- Toshimitsu Araki
- Yasuhiro Inoue
- Yasuhiko Mohri
- Masato Kusunoki
View Affiliations

Affiliations: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan
Published online on: October 7, 2020 https://doi.org/10.3892/ol.2020.12196
Article Number: 333
Copyright: © Mori et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Accumulating evidence suggests that overexpression of heat shock protein 47 (HSP47) increases cancer progression, and that HSP47 level in the tumor‑associated stroma may serve as a diagnostic marker in various cancers. The present study aimed to evaluate whether HSP47 gene expression in colorectal cancer (CRC) tissues could be used to identify lymph node (LN) metastasis status preoperatively in patients with CRC. To do so, HSP47 gene expression was determined and its association with the clinicopathological characteristics of patients with CRC was analyzed. A total of 139 surgical specimens from patients with CRC and 36 patients with benign colonic disease undergoing surgery at Mie University Hospital were analyzed. HSP47 gene expression was determined by reverse transcription quantitative PCR using Power SYBR Green PCR methods. Expression level of HSP47 was significantly higher in CRC tissues compared with normal tissue from patients with benign colonic disease. Furthermore, high HSP47 expression was significantly associated with tumor progression, including high T stage, lymph node metastasis and venous invasion, and high TNM stage. High HSP47 expression may therefore serve as a novel predictive biomarker for determining patients with CRC and LN metastasis. According to Kaplan‑Meier analysis, patients with high HSP47 expression level had significantly poorer overall survival than those with low HSP47 expression level. Furthermore, multivariate analyses identified HSP47 expression as an independent predictive marker for LN metastasis and poor overall survival in patients with CRC. In summary, the present study demonstrated that HSP47 expression may be considered as a novel biomarker for predicting LN metastasis status and prognosis in patients with CRC.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Edge S, Compton C, Fritz A, Greene F and Trotti A: AJCC Cancer Staging Manual. 7th. Springer; New York, NY: pp. 237–46. 2010
3	Chau I and Cunningham D: Adjuvant therapy in colon cancer: Current status and future directions. Cancer Treat Rev. 28:223–236. 2002. View Article : Google Scholar : PubMed/NCBI
4	Schrag D, Gelfand SE, Bach PB, Guillem J, Minsky BD and Begg CB: Who gets adjuvant treatment for stage II and III rectal cancer? Insight from surveillance, epidemiology, and end results-Medicare. J Clin Oncol. 19:3712–3718. 2001. View Article : Google Scholar : PubMed/NCBI
5	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
6	Kwak JY, Kim JS, Kim HJ, Ha HK, Yu CS and Kim JC: Diagnostic value of FDG-PET/CT for lymph node metastasis of colorectal cancer. World J Surg. 36:1898–1905. 2012. View Article : Google Scholar : PubMed/NCBI
7	Low G, Tho LM, Leen E, Wiebe E, Kakumanu S, McDonald AC and Poon FW: The role of imaging in the pre-operative staging and post-operative follow-up of rectal cancer. Surgeon. 6:222–231. 2008. View Article : Google Scholar : PubMed/NCBI
8	Imaoka H, Toiyama Y, Saigusa S, Kawamura M, Kawamoto A, Okugawa Y, Hiro J, Tanaka K, Inoue Y, Mohri Y and Kusunoki M: RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis. 36:346–354. 2015. View Article : Google Scholar : PubMed/NCBI
9	Imaoka H, Toiyama Y, Fujikawa H, Hiro J, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Mori T, Kato T, et al: Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer. Ann Oncol. 27:1879–1886. 2016. View Article : Google Scholar : PubMed/NCBI
10	Lina O, Marie-Louise H, Anne I, Gudrun L and Sten H: Allocating colorectal cancer patients to different risk categories by using a five-biomarker mRNA combination in lymph node analysis. PLoS One. 15:e02290072020. View Article : Google Scholar : PubMed/NCBI
11	Li H, Ma SQ, Huang J, Chen XP and Zhou HH: Roles of long noncoding RNAs in colorectal cancer metastasis. Oncotarget. 8:39859–39876. 2017. View Article : Google Scholar : PubMed/NCBI
12	Mori K, Toiyama Y, Otake K, Fujikawa H, Saigusa S, Hiro J, Kobayashi M, Ohi M, Tanaka K, Inoue Y, et al: Proteomics analysis of differential protein expression identifies heat shock protein 47 as a predictive marker for lymph node metastasis in patients with colorectal cancer. Int J Cancer. 140:1425–1435. 2017. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Japanese Society for Cancer of the Colon and Rectum General Rules for Clinical and Pathological Studies on Cancer of the Colon RaARV. (7th). (in Japanese). (Tokyo). 36–37. 2009.
15	Nagata K, Saga S and Yamada KM: A major collagen-binding protein of chick embryo fibroblasts is a novel heat shock protein. J Cell Biol. 103:223–229. 1986. View Article : Google Scholar : PubMed/NCBI
16	Kurkinen M, Taylor A, Garrels JI and Hogan BL: Cell surface-associated proteins which bind native type IV collagen or gelatin. J Biol Chem. 259:5915–5922. 1984.PubMed/NCBI
17	Schlesinger MJ: Heat shock proteins. J Biol Chem. 265:12111–12114. 1990.PubMed/NCBI
18	Satoh M, Hirayoshi K, Yokota S, Hosokawa N and Nagata K: Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen. J Cell Biol. 133:469–483. 1996. View Article : Google Scholar : PubMed/NCBI
19	Nakai A, Satoh M, Hirayoshi K and Nagata K: Involvement of the stress protein HSP47 in procollagen processing in the endoplasmic reticulum. J Cell Biol. 117:903–914. 1992. View Article : Google Scholar : PubMed/NCBI
20	Kawada N, Kuroki T, Kobayashi K, Inoue M, Nakatani K, Kaneda K and Nagata K: Expression of heat-shock protein 47 in mouse liver. Cell Tissue Res. 284:341–346. 1996. View Article : Google Scholar : PubMed/NCBI
21	Razzaque MS, Nazneen A and Taguchi T: Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases. Mod Pathol. 11:1183–1188. 1998.PubMed/NCBI
22	Razzaque MS, Kumatori A, Harada T and Taguchi T: Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy. Nephron. 80:434–443. 1998. View Article : Google Scholar : PubMed/NCBI
23	Kuroda K, Tsukifuji R and Shinkai H: Increased expression of heat-shock protein 47 is associated with overproduction of type I procollagen in systemic sclerosis skin fibroblasts. J Invest Dermatol. 111:1023–1028. 1998. View Article : Google Scholar : PubMed/NCBI
24	Naitoh M, Hosokawa N, Kubota H, Tanaka T, Shirane H, Sawada M, Nishimura Y and Nagata K: Upregulation of HSP47 and collagen type III in the dermal fibrotic disease, keloid. Biochem Biophys Res Commun. 280:1316–1322. 2001. View Article : Google Scholar : PubMed/NCBI
25	Sauk JJ, Nikitakis N and Siavash H: Hsp47 a novel collagen binding serpin chaperone, autoantigen and therapeutic target. Front Biosci. 10:107–118. 2005. View Article : Google Scholar : PubMed/NCBI
26	Morino M, Tsuzuki T, Iijima H, Shirakami T, Kiyosuke YI, Ishikawa Y, Yoshimura M and Yoshikumi C: Marked induction of HSP47, a collagen-binding stress protein, during solid tumor formation of ascitic Sarcoma 180 in vivo. In Vivo. 9:503–508. 1995.PubMed/NCBI
27	Lee HW, Kwon J, Kang MC, Noh MK, Koh JS, Kim JH and Park JH: Overexpression of HSP47 in esophageal squamous cell carcinoma: Clinical implications and functional analysis. Dis Esophagus. 29:848–855. 2016. View Article : Google Scholar : PubMed/NCBI
28	Araki K, Mikami T, Yoshida T, Kikuchi M, Sato Y, Oh-ishi M, Kodera Y, Maeda T and Okayasu I: High expression of HSP47 in ulcerative colitis-associated carcinomas: Proteomic approach. Br J Cancer. 101:492–497. 2009. View Article : Google Scholar : PubMed/NCBI
29	Maitra A, Iacobuzio-Donahue C, Rahman A, Sohn TA, Argani P, Meyer R, Yeo CJ, Cameron JL, Goggins M, Kern SE, et al: Immunohistochemical validation of a novel epithelial and a novel stromal marker of pancreatic ductal adenocarcinoma identified by global expression microarrays: Sea urchin fascin homolog and heat shock protein 47. Am J Clin Pathol. 118:52–59. 2002. View Article : Google Scholar : PubMed/NCBI
30	Yamamoto N, Kinoshita T, Nohata N, Yoshino H, Itesako T, Fujimura L, Mitsuhashi A, Usui H, Enokida H, Nakagawa M, et al: Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma. Int J Oncol. 43:1855–1863. 2013. View Article : Google Scholar : PubMed/NCBI
31	Morino M, Tsuzuki T, Ishikawa Y, Shirakami T, Yoshimura M, Kiyosuke Y, Matsunaga K, Yoshikumi C and Saijo N: Specific expression of HSP47 in human tumor cell lines in vitro. In Vivo. 11:17–21. 1997.PubMed/NCBI
32	Krishnamurthi SS, Seo Y and Kinsella TJ: Adjuvant therapy for rectal cancer. Clin Colon Rectal Surg. 20:167–181. 2007. View Article : Google Scholar : PubMed/NCBI
33	Greene FL PD, Fleming I and Fritz A: AJCC Cancer Staging Manual. 6th. Springer-Verlag; Berlin: 2002, View Article : Google Scholar