Clinical significance of ribosomal protein S15 expression in patients with colorectal cancer liver metastases.
RPS15
apoptosis
colorectal cancer
liver metastasis
Journal
Journal of hepato-biliary-pancreatic sciences
ISSN: 1868-6982
Titre abrégé: J Hepatobiliary Pancreat Sci
Pays: Japan
ID NLM: 101528587
Informations de publication
Date de publication:
04 Jun 2024
04 Jun 2024
Historique:
medline:
5
6
2024
pubmed:
5
6
2024
entrez:
5
6
2024
Statut:
aheadofprint
Résumé
Liver metastasis is the most frequently observed distant metastasis of colorectal cancer, and the residual liver recurrence rate after hepatic resection is still high. To explore the mechanism of liver metastasis to discover potential new treatments, we assessed the relationship between the expression of differentially expressed genes (DEGs) and prognosis in patients with colorectal cancer liver metastasis (CRLM). The gene expression dataset was extracted from The Cancer Genome Atlas and the Gene Expression Omnibus. Significance analysis of DEGs between tumor and normal samples of colorectum, liver, and lung was conducted. A total of 80 CRLM patients were studied to assess the expression of RPS15, characteristics, and outcomes. We examined the relationships of RPS15 expression to cell viability and apoptosis in vitro and vivo. Significance analysis identified 33 DEGs. In our cohorts, the overall survival rates were significantly lower in the high-RPS15-expression group, and high expression of RPS15 was an independent and unfavorable prognostic factor in recurrence-free survival and overall survival. Knockdown of RPS15 expression reduced the proliferative capacity of colorectal cancer cells and increased BAX-induced apoptotic cell death. RPS15 expression is an independent prognostic factor for CRLM patients and might be a novel therapeutic target for CRLM.
Sections du résumé
BACKGROUND
BACKGROUND
Liver metastasis is the most frequently observed distant metastasis of colorectal cancer, and the residual liver recurrence rate after hepatic resection is still high. To explore the mechanism of liver metastasis to discover potential new treatments, we assessed the relationship between the expression of differentially expressed genes (DEGs) and prognosis in patients with colorectal cancer liver metastasis (CRLM).
METHODS
METHODS
The gene expression dataset was extracted from The Cancer Genome Atlas and the Gene Expression Omnibus. Significance analysis of DEGs between tumor and normal samples of colorectum, liver, and lung was conducted. A total of 80 CRLM patients were studied to assess the expression of RPS15, characteristics, and outcomes. We examined the relationships of RPS15 expression to cell viability and apoptosis in vitro and vivo.
RESULTS
RESULTS
Significance analysis identified 33 DEGs. In our cohorts, the overall survival rates were significantly lower in the high-RPS15-expression group, and high expression of RPS15 was an independent and unfavorable prognostic factor in recurrence-free survival and overall survival. Knockdown of RPS15 expression reduced the proliferative capacity of colorectal cancer cells and increased BAX-induced apoptotic cell death.
CONCLUSIONS
CONCLUSIONS
RPS15 expression is an independent prognostic factor for CRLM patients and might be a novel therapeutic target for CRLM.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Journal of Hepato‐Biliary‐Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.
Références
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.
Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67:177–193.
Engstrand J, Nilsson H, Strömberg C, Jonas E, Freedman J. Colorectal cancer liver metastases—a population‐based study on incidence, management and survival. BMC Cancer. 2018;18:78.
Noda T, Takahashi H, Tei M, Nishida N, Hata T, Takeda Y, et al. Clinical outcomes of neoadjuvant chemotherapy for resectable colorectal liver metastasis with intermediate risk of postoperative recurrence: a multi‐institutional retrospective study. Ann Gastroenterol Surg. 2023;7:479–490.
Lintoiu‐Ursut B, Tulin A, Constantinoiu S. Recurrence after hepatic resection in colorectal cancer liver metastasis—review article. J Med Life. 2015;8:12–14.
Noda T, Eguchi H, Wada H, Iwagami Y, Yamada D, Asaoka T, et al. Short‐term surgical outcomes of minimally invasive repeat hepatectomy for recurrent liver cancer. Surg Endosc. 2018;32:46–52.
Chen H, Xiao Q, Hu Y, Chen L, Jiang K, Tang Y, et al. ANGPTL1 attenuates colorectal cancer metastasis by up‐regulating microRNA‐138. J Exp Clin Cancer Res. 2017;36:78.
Jiang K, Chen H, Fang Y, Chen L, Zhong C, Bu T, et al. Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness. J Exp Clin Cancer Res. 2021;40:21.
Sakano Y, Noda T, Kobayashi S, Sasaki K, Iwagami Y, Yamada D, et al. Tumor endothelial cell‐induced CD8(+) T‐cell exhaustion via GPNMB in hepatocellular carcinoma. Cancer Sci. 2022;113:1625–1638.
Sakano Y, Noda T, Kobayashi S, Kitagawa A, Iwagami Y, Yamada D, et al. Clinical significance of acylphosphatase 1 expression in combined HCC‐iCCA, HCC, and iCCA. Dig Dis Sci. 2021;67:3817–3830.
Noda T, Yamamoto H, Takemasa I, Yamada D, Uemura M, Wada H, et al. PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection. Liver Int. 2012;32:110–118.
Yokota Y, Noda T, Okumura Y, Kobayashi S, Iwagami Y, Yamada D, et al. Serum exosomal miR‐638 is a prognostic marker of HCC via downregulation of VE‐cadherin and ZO‐1 of endothelial cells. Cancer Sci. 2021;112:1275–1288.
Matsumoto K, Noda T, Kobayashi S, Sakano Y, Yokota Y, Iwagami Y, et al. Inhibition of glycolytic activator PFKFB3 suppresses tumor growth and induces tumor vessel normalization in hepatocellular carcinoma. Cancer Lett. 2021;500:29–40.
Kato K, Noda T, Kobayashi S, Sasaki K, Iwagami Y, Yamada D, et al. KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. Cancer Sci. 2024;115:1520–1535.
Maruyama K, Tominaga T, Nonaka T, Moriyama M, Oyama S, Ishii M, et al. Efficacy of risk‐stratified indicators for adjuvant chemotherapy with fluorouracil and oxaliplatin after hepatectomy for colorectal cancer liver metastasis. Int J Color Dis. 2022;37:1545–1552.
Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol. 1986;150:195–203.
Esmatabadi MJ, Bakhshinejad B, Motlagh FM, Babashah S, Sadeghizadeh M. Therapeutic resistance and cancer recurrence mechanisms: unfolding the story of tumour coming back. J Biosci. 2016;41:497–506.
Saha S, Philimon B, Efeson M, Helina A, Elgamal M, Kiya G, et al. The role of sentinel lymph node mapping in colon cancer: detection of micro‐metastasis, effect on survival, and driver of a paradigm shift in extent of colon resection. Clin Exp Metastasis. 2022;39:109–115.
Zhang F, Zhang Y, Zhao W, Deng K, Wang Z, Yang C, et al. Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review. Oncotarget. 2017;8:35460–35472.
Murray NP, Villalon R, Orrego S, Guzman E. The association of the neutrophil‐lymphocyte ratio with the presence of minimal residual disease and outcome in patients with stage II colon cancer treated with surgery alone. Color Dis. 2021;23:805–813.
Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ. In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia. 1999;1:50–62.
Zhao Y, Li Y, Zhu R, Feng R, Cui H, Yu X, et al. RPS15 interacted with IGF2BP1 to promote esophageal squamous cell carcinoma development via recognizing m(6)a modification. Signal Transduct Target Ther. 2023;8:224.
Goudarzi KM, Lindström MS. Role of ribosomal protein mutations in tumor development (review). Int J Oncol. 2016;48:1313–1324.
Robledo S, Idol RA, Crimmins DL, Ladenson JH, Mason PJ, Bessler M. The role of human ribosomal proteins in the maturation of rRNA and ribosome production. RNA. 2008;14:1918–1929.
Pecoraro A, Pagano M, Russo G, Russo A. Ribosome biogenesis and cancer: overview on ribosomal proteins. Int J Mol Sci. 2021;22:5496.
Nieminen TT, O'Donohue MF, Wu Y, Lohi H, Scherer SW, Paterson AD, et al. Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency. Gastroenterology. 2014;147:595–598.e5.
Mitterer V, Shayan R, Ferreira‐Cerca S, Murat G, Enne T, Rinaldi D, et al. Conformational proofreading of distant 40S ribosomal subunit maturation events by a long‐range communication mechanism. Nat Commun. 2019;10:2754.
Shen C, Chen Z, Zhang Y, Xu W, Peng R, Jiang J, et al. Biochemical and clinical effects of RPS20 expression in renal clear cell carcinoma. Oncol Rep. 2023;49:1–13.
Rössler I, Weigl S, Fernández‐Fernández J, Martín‐Villanueva S, Strauss D, Hurt E, et al. The C‐terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre‐40S maturation. RNA Biol. 2022;19:560–574.
Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889;133:571–573.
Berman RS, Portera CA Jr, Ellis LM. Biology of liver metastases. Cancer Treat Res. 2001;109:183–206.