Skip to main content
Erschienen in: Tumor Biology 10/2014

01.10.2014 | Research Article

CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients

verfasst von: Cong Li, Zhimin Wang, Fangqi Liu, Ji Zhu, Li Yang, Guoxiang Cai, Zhen Zhang, Wei Huang, Sanjun Cai, Ye Xu

Erschienen in: Tumor Biology | Ausgabe 10/2014

Einloggen, um Zugang zu erhalten

Abstract

Chemoradiotherapy has been commonly used as neoadjuvant therapy for rectal cancer to allow for less aggressive surgical approaches and to improve quality of life. In cancer, it has been reported that CXCL10 has an anti-tumor function. However, the association between CXCL10 and chemoradiosensitivity has not been fully investigated. We performed this study to investigate the relationship between CXCL10 expression and chemoradiosensitivity in rectal cancer patients. Ninety-five patients with rectal cancer who received neoadjuvant chemoradiotherapy (NCRT) were included. Clinical parameters were compared with the outcome of NCRT and CXCL10 messenger RNA (mRNA) expression between the pathological complete response (pCR) group and non-pathological complete response (npCR) group. CXCL10 mRNA and protein expressions between groups were analyzed using the Student’s t test and chi-square test. The mean mRNA level of CXCL10 in the pCR group was significantly higher than that in the npCR group (p = 0.010). In the pCR group, 73.7 % of the patients had high CXCL10 mRNA expression, and 61.4 % of the patients in the npCR group had low CXCL10 mRNA expression. Subjects with high CXCL10 mRNA expression demonstrated a higher sensitivity to NCRT (p = 0.011). The receiver operating characteristic curve showed that the diagnostic performance of CXCL10 mRNA expression had an area under the curve of 0.720 (95 % confidence interval, 0.573–0.867). There were no differences between the pCR and npCR groups in CXCL10 protein expression (p > 0.05). High CXCL10 mRNA expression is associated with a better tumor response to NCRT in rectal cancer patients and may predict the outcome of NCRT in this malignancy.
Literatur
1.
Zurück zum Zitat Dedemadi G, Wexner SD. Complete response after neoadjuvant therapy in rectal cancer: to operate or not to operate? Dig Dis. 2012;30 Suppl 2:109–17.CrossRefPubMed Dedemadi G, Wexner SD. Complete response after neoadjuvant therapy in rectal cancer: to operate or not to operate? Dig Dis. 2012;30 Suppl 2:109–17.CrossRefPubMed
2.
Zurück zum Zitat Toiyama Y, Fujikawa H, Kawamura M, Matsushita K, Saigusa S, Tanaka K, et al. Evaluation of CXCL10 as a novel serum marker for predicting liver metastasis and prognosis in colorectal cancer. Int J Oncol. 2012;40:560–6.PubMed Toiyama Y, Fujikawa H, Kawamura M, Matsushita K, Saigusa S, Tanaka K, et al. Evaluation of CXCL10 as a novel serum marker for predicting liver metastasis and prognosis in colorectal cancer. Int J Oncol. 2012;40:560–6.PubMed
3.
Zurück zum Zitat Zipin-Roitman A, Meshel T, Sagi-Assif O, Shalmon B, Avivi C, Pfeffer RM, et al. CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. Cancer Res. 2007;67:3396–405.CrossRefPubMed Zipin-Roitman A, Meshel T, Sagi-Assif O, Shalmon B, Avivi C, Pfeffer RM, et al. CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. Cancer Res. 2007;67:3396–405.CrossRefPubMed
4.
Zurück zum Zitat Jiang Z, Xu Y, Cai S. CXCL10 expression and prognostic significance in stage II and III colorectal cancer. Mol Biol Rep. 2010;37:3029–36.CrossRefPubMed Jiang Z, Xu Y, Cai S. CXCL10 expression and prognostic significance in stage II and III colorectal cancer. Mol Biol Rep. 2010;37:3029–36.CrossRefPubMed
5.
Zurück zum Zitat Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys. 1999;44:1027–38.CrossRefPubMed Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys. 1999;44:1027–38.CrossRefPubMed
6.
Zurück zum Zitat Agostini M, Pucciarelli S, Enzo MV, Del Bianco P, Briarava M, Bedin C, et al. Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann Surg Oncol. 2011;18:2461–8.CrossRefPubMed Agostini M, Pucciarelli S, Enzo MV, Del Bianco P, Briarava M, Bedin C, et al. Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann Surg Oncol. 2011;18:2461–8.CrossRefPubMed
7.
Zurück zum Zitat Jao SW, Chen SF, Lin YS, Chang YC, Lee TY, Wu CC, et al. Cytoplasmic CD133 expression is a reliable prognostic indicator of tumor regression after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer. Ann Surg Oncol. 2012;19:3432–40.CrossRefPubMed Jao SW, Chen SF, Lin YS, Chang YC, Lee TY, Wu CC, et al. Cytoplasmic CD133 expression is a reliable prognostic indicator of tumor regression after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer. Ann Surg Oncol. 2012;19:3432–40.CrossRefPubMed
8.
Zurück zum Zitat Pucciarelli S, Rampazzo E, Briarava M, Maretto I, Agostini M, Digito M, et al. Telomere-specific reverse transcriptase (hTERT) and cell-free RNA in plasma as predictors of pathologic tumor response in rectal cancer patients receiving neoadjuvantchemoradiotherapy. Ann Surg Oncol. 2012;19:3089–96.CrossRefPubMed Pucciarelli S, Rampazzo E, Briarava M, Maretto I, Agostini M, Digito M, et al. Telomere-specific reverse transcriptase (hTERT) and cell-free RNA in plasma as predictors of pathologic tumor response in rectal cancer patients receiving neoadjuvantchemoradiotherapy. Ann Surg Oncol. 2012;19:3089–96.CrossRefPubMed
9.
Zurück zum Zitat Stoehlmacher J, Goekkurt E, Mogck U, Aust DE, Kramer M, Baretton GB, et al. Thymidylate synthase genotypes and tumour regression in stage II/III rectal cancer patients after neoadjuvant fluorouracil-based chemoradiation. Cancer Lett. 2008;272:221–5.CrossRefPubMed Stoehlmacher J, Goekkurt E, Mogck U, Aust DE, Kramer M, Baretton GB, et al. Thymidylate synthase genotypes and tumour regression in stage II/III rectal cancer patients after neoadjuvant fluorouracil-based chemoradiation. Cancer Lett. 2008;272:221–5.CrossRefPubMed
10.
Zurück zum Zitat Kim J, Kim J, Li S, Yoon W, Song K, Kim K, et al. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2006;66:195–200.CrossRefPubMed Kim J, Kim J, Li S, Yoon W, Song K, Kim K, et al. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2006;66:195–200.CrossRefPubMed
11.
Zurück zum Zitat Nishioka M, Shimada M, Kurita N, Iwata T, Morimoto S, Yoshikawa K, et al. Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer. Cancer Genomics Proteomics. 2011;8:87–92.PubMed Nishioka M, Shimada M, Kurita N, Iwata T, Morimoto S, Yoshikawa K, et al. Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer. Cancer Genomics Proteomics. 2011;8:87–92.PubMed
12.
Zurück zum Zitat Rimkus C, Friederichs J, Boulesteix AL, Theisen J, Mages J, Becker K, et al. Microarray-based prediction of tumor response to neoadjuvantradiochemotherapy of patients with locally advanced rectal cancer. Clin Gastroenterol Hepatol. 2008;6:53–61.CrossRefPubMed Rimkus C, Friederichs J, Boulesteix AL, Theisen J, Mages J, Becker K, et al. Microarray-based prediction of tumor response to neoadjuvantradiochemotherapy of patients with locally advanced rectal cancer. Clin Gastroenterol Hepatol. 2008;6:53–61.CrossRefPubMed
13.
Zurück zum Zitat Casado E, Moreno Garcia V, Javier Sanchez J, Blanco M, Maurel J, Feliu J, et al. A combined strategy of SAGE and quantitative PCR provides a 13-Gene signature that predicts preoperative chemoradiotherapy response and outcome in rectal cancer. Clin Cancer Res. 2011;17:4145–54.CrossRefPubMed Casado E, Moreno Garcia V, Javier Sanchez J, Blanco M, Maurel J, Feliu J, et al. A combined strategy of SAGE and quantitative PCR provides a 13-Gene signature that predicts preoperative chemoradiotherapy response and outcome in rectal cancer. Clin Cancer Res. 2011;17:4145–54.CrossRefPubMed
14.
Zurück zum Zitat Yates-Binder CC, Rodgers M, Jaynes J, Wells A, Bodnar RJ, Turner T. An IP-10 (CXCL10)-derived peptide inhibits angiogenesis. PLoS One. 2012;7:e40812.PubMedCentralCrossRefPubMed Yates-Binder CC, Rodgers M, Jaynes J, Wells A, Bodnar RJ, Turner T. An IP-10 (CXCL10)-derived peptide inhibits angiogenesis. PLoS One. 2012;7:e40812.PubMedCentralCrossRefPubMed
15.
Zurück zum Zitat Sato E, Fujimoto J, Toyoki H, Sakaguchi H, Alam SM, Jahan I, et al. Expression of IP-10 related to angiogenesis in uterine cervical cancers. Br J Cancer. 2007;96:1735–9.PubMedCentralCrossRefPubMed Sato E, Fujimoto J, Toyoki H, Sakaguchi H, Alam SM, Jahan I, et al. Expression of IP-10 related to angiogenesis in uterine cervical cancers. Br J Cancer. 2007;96:1735–9.PubMedCentralCrossRefPubMed
16.
Zurück zum Zitat Petrai I, Rombouts K, Lasagni L, Annunziato F, Cosmi L, Romanelli RG, et al. Activation of p38MAPK mediates the angiostatic effect of the chemokine receptor CXCR3-B. Int J Biochem Cell Biol. 2008;40:1764–74.CrossRefPubMed Petrai I, Rombouts K, Lasagni L, Annunziato F, Cosmi L, Romanelli RG, et al. Activation of p38MAPK mediates the angiostatic effect of the chemokine receptor CXCR3-B. Int J Biochem Cell Biol. 2008;40:1764–74.CrossRefPubMed
17.
Zurück zum Zitat Lee CG, Heijn M, di Tomaso E, Griffon-Etienne G, Ancukiewicz M, Koike C, et al. Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res. 2000;60:5565–70.PubMed Lee CG, Heijn M, di Tomaso E, Griffon-Etienne G, Ancukiewicz M, Koike C, et al. Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res. 2000;60:5565–70.PubMed
18.
Zurück zum Zitat Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res. 2004;64:3731–6.CrossRefPubMed Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res. 2004;64:3731–6.CrossRefPubMed
19.
Zurück zum Zitat Yang F, Gou M, Deng H, Yi T, Zhong Q, Wei Y, et al. Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneiminenanogels. Oncol Rep. 2012;28:668–76.PubMed Yang F, Gou M, Deng H, Yi T, Zhong Q, Wei Y, et al. Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneiminenanogels. Oncol Rep. 2012;28:668–76.PubMed
20.
Zurück zum Zitat Koukourakis MI. Tumour angiogenesis and response to radiotherapy. Anticancer Res. 2001;21:4285–300.PubMed Koukourakis MI. Tumour angiogenesis and response to radiotherapy. Anticancer Res. 2001;21:4285–300.PubMed
21.
Zurück zum Zitat Wachsberger P, Burd R, Dicker AP. Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: exploring mechanisms of interaction. Clin Cancer Res. 2003;9:1957–71.PubMed Wachsberger P, Burd R, Dicker AP. Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: exploring mechanisms of interaction. Clin Cancer Res. 2003;9:1957–71.PubMed
22.
Zurück zum Zitat Yang LL, Wang BQ, Chen LL, Luo HQ, Wu JB. CXCL10 enhances radiotherapy effects in HeLa cells through cell cycle redistribution. Oncol Lett. 2012;3:383–6.PubMedCentralPubMed Yang LL, Wang BQ, Chen LL, Luo HQ, Wu JB. CXCL10 enhances radiotherapy effects in HeLa cells through cell cycle redistribution. Oncol Lett. 2012;3:383–6.PubMedCentralPubMed
23.
Zurück zum Zitat Rentoft M, Coates PJ, Loljung L, Wilms T, Laurell G, Nylander K. Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue. Tumour Biol. 2014;35:4191–8.PubMedCentralCrossRefPubMed Rentoft M, Coates PJ, Loljung L, Wilms T, Laurell G, Nylander K. Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue. Tumour Biol. 2014;35:4191–8.PubMedCentralCrossRefPubMed
24.
Zurück zum Zitat Stark AM, Pfannenschmidt S, Tscheslog H, Maass N, Rosel F, Mehdorn HM, et al. Reduced mRNA and protein expression of BCL-2 versus decreased mRNA and increased protein expression of BAX in breast cancer brain metastases: a real-time PCR and immunohistochemical evaluation. Neurol Res. 2006;28:787–93.CrossRefPubMed Stark AM, Pfannenschmidt S, Tscheslog H, Maass N, Rosel F, Mehdorn HM, et al. Reduced mRNA and protein expression of BCL-2 versus decreased mRNA and increased protein expression of BAX in breast cancer brain metastases: a real-time PCR and immunohistochemical evaluation. Neurol Res. 2006;28:787–93.CrossRefPubMed
25.
Zurück zum Zitat Chong YM, Williams SL, Elkak A, Sharma AK, Mokbel K. Insulin-like growth factor 1 (IGF-1) and its receptor mRNA levels in breast cancer and adjacent non-neoplastic tissue. Anticancer Res. 2006;26:167–73.PubMed Chong YM, Williams SL, Elkak A, Sharma AK, Mokbel K. Insulin-like growth factor 1 (IGF-1) and its receptor mRNA levels in breast cancer and adjacent non-neoplastic tissue. Anticancer Res. 2006;26:167–73.PubMed
26.
Zurück zum Zitat Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13:227–32.PubMedCentralPubMed Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13:227–32.PubMedCentralPubMed
Metadaten
Titel
CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients
verfasst von
Cong Li
Zhimin Wang
Fangqi Liu
Ji Zhu
Li Yang
Guoxiang Cai
Zhen Zhang
Wei Huang
Sanjun Cai
Ye Xu
Publikationsdatum
01.10.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 10/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2234-0

Weitere Artikel der Ausgabe 10/2014

Tumor Biology 10/2014 Zur Ausgabe

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

27.05.2024 Blut im Stuhl Nachrichten

Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.

Mammakarzinom: Brustdichte beeinflusst rezidivfreies Überleben

26.05.2024 Mammakarzinom Nachrichten

Frauen, die zum Zeitpunkt der Brustkrebsdiagnose eine hohe mammografische Brustdichte aufweisen, haben ein erhöhtes Risiko für ein baldiges Rezidiv, legen neue Daten nahe.

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.