Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 16;11(5):420.
doi: 10.3390/jpm11050420.

Lincp21-RNA as Predictive Response Marker for Preoperative Chemoradiotherapy in Rectal Cancer

Jose Carlos Benitez  1   2 , Marc Campayo  2 , Tania Díaz  3 , Carme Ferrer  4 , Melissa Acosta-Plasencia  3 , Mariano Monzo  3 , Luis Cirera  2 , Benjamin Besse  1   5 , Alfons Navarro  3
Affiliations

Lincp21-RNA as Predictive Response Marker for Preoperative Chemoradiotherapy in Rectal Cancer

Jose Carlos Benitez et al. J Pers Med. .

Abstract

Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients, but its use in non-responders can be associated with increased toxicities and resection delay. LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation. We aimed to study whether lincRNA-p21 expression levels can act as a predictive biomarker for neoadjuvant CRT response. We analyzed RNAs from pretreatment biopsies from 70 RC patients treated with preoperative CRT. Pathological response was classified according to the tumor regression grade (TRG) Dworak classification. LincRNA-p21 expression was determined by RTqPCR. The results showed that lincRNA-p21 was upregulated in stage III tumors (p = 0.007) and in tumors with the worst response regarding TRG (p = 0.027) and downstaging (p = 0.016). ROC curve analysis showed that lincRNA-p21 expression had the capacity to distinguish a complete response from others (AUC:0.696; p = 0.014). LincRNA-p21 was shown as an independent marker of preoperative CRT response (p = 0.047) and for time to relapse (TTR) (p = 0.048). In conclusion, lincRNA-p21 is a marker of advanced disease, worse response to neoadjuvant CRT, and shorter TTR in locally advanced RC patients. The study of lincRNA-p21 may be of value in the individualization of pre-operative CRT in RC.

Keywords: chemoradiotherapy; colorectal cancer; lincRNA-p21; long non-coding RNA; p53; predictive biomarker; rectal cancer.

PubMed Disclaimer

Conflict of interest statement

All of the authors have reviewed and approved this version of the manuscript and agree with the decision to submit. None of the authors declare any conflicts of interest.

Figures

Figure 1
Figure 1
LincRNA-p21 levels and clinicopathological characteristics. (A) LincRNA-p21 expression in (A) stage III vs. stage II; (B) ypT0 vs. ypT-1–2 vs. ypT3–4; (C) ypN0 vs. ypN1–2; (D) ypT0N0 vs. I-II vs. III; (E) downstaging no vs. yes; (F) TRG 0–3 vs. TRG 4.
Figure 2
Figure 2
Predictive analyses for response to neoadjuvant treatment. (A) ROC curve analyses to evaluate the potential utility of lincRNA-p21 to distinguish patients with maximum response to neoadjuvant treatment (TRG4) from others (TRG 0–3). (B) Percentage of patients with each TRG according to low vs. high lincRNA-p21 expression, dichotomized using optimum truncation point obtained in the ROC curve analysis (−0.1). AUC, area under the curve. TRG, tumor regression grade.
Figure 3
Figure 3
Kaplan–Meier curves for time to relapse (TTR) (A) and overall survival (OS) (B) according to lincRNA-p21 expression levels in 70 rectal cancer patients. The log-rank test was used to calculate whether significant differences in survival times between high or low lincRNA-p21 levels were achieved.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020;70:7–30. doi: 10.3322/caac.21590. - DOI - PubMed
    1. Wei E.K., Giovannucci E., Wu K., Rosner B., Fuchs C.S., Willett W.C., Colditz G.A. Comparison of risk factors for colon and rectal cancer. Int. J. Cancer. 2003;108:433–442. doi: 10.1002/ijc.11540. - DOI - PMC - PubMed
    1. Kirkegaard H., Johnsen N.F., Christensen J., Frederiksen K., Overvad K., Tjønneland A. Association of adherence to lifestyle recommendations and risk of colorectal cancer: A prospective Danish cohort study. BMJ. 2010;341:c5504. doi: 10.1136/bmj.c5504. - DOI - PMC - PubMed
    1. Guinney J., Dienstmann R., Wang X., De Reyniès A., Schlicker A., Soneson C., Marisa L., Roepman P., Nyamundanda G., Angelino P., et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 2015;21:1350–1356. doi: 10.1038/nm.3967. - DOI - PMC - PubMed
    1. Bosset J.-F., Calais G., Mineur L., Maingon P., Stojanovic-Rundic S., Bensadoun R.-J., Bardet E., Beny A., Ollier J.-C., Bolla M., et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: Long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–190. doi: 10.1016/S1470-2045(13)70599-0. - DOI - PubMed