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Peer-reviewedCC BY-NC-NDCancer cell international

High xCT expression indicates poor prognosis and chemoradiotherapy resistance in rectal cancer patients.

  • Yingru Li1,2,3
  • Heng LiuFu1,2,3
  • Zhilong Yuan1,2,3
  • Wenchang Gan1,2,3
  • Shaoyong Peng1,2,3
  • Jinhong Li4
  • Haiyang Xin4
  • Canfeng Cai5
  • Bing Zeng6,7,8
8 affiliations
  1. 1Department of General Surgery, Hernia and Abdominal Wall Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, P.R. China.
  2. 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, P.R. China.
  3. 3Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, P.R. China.
  4. 4Affiliated Qingyuan Hospital, The Sixth Clinical Medical School, Qingyuan People's Hospital, Guangzhou Medical University, Qing yuan, 511518, Guangdong, P.R. China.
  5. 5Affiliated Qingyuan Hospital, The Sixth Clinical Medical School, Qingyuan People's Hospital, Guangzhou Medical University, Qing yuan, 511518, Guangdong, P.R. China. [email protected].
  6. 6Department of General Surgery, Hernia and Abdominal Wall Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, P.R. China. [email protected].
  7. 7Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, P.R. China. [email protected].
  8. 8Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, P.R. China. [email protected].
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Abstract

Background

xCT/SLC7A11, an amino acid transporter, is implicated in various cancers. However, its role in rectal cancer remains unclear. This study aimed to explore its predictive value for prognosis and chemoradiotherapy response in rectal cancer patients.Methods and materials

xCT expression was assessed using immunohistochemistry and RT-qPCR, and its associations with clinicopathological features and prognosis were analyzed. Single-cell RNA sequencing data and the TIMER platform were used to examine xCT's correlation with immune cell infiltration. A prognostic nomogram model was developed and evaluated with ROC, calibration, and decision curve analysis. Cell proliferation and cytotoxicity assays were conducted to assess xCT's role in ferroptosis and chemoradiotherapy sensitivity.Results

xCT expression was elevated in rectal cancer tissues and correlated with adverse clinicopathological features, including tumor regression grade (P < 0.001). Single-cell and immune infiltration analyses indicated that xCT was associated with the immune microenvironment. High xCT expression predicted worse overall and disease-free survival, and multivariate analysis confirmed it as an independent prognostic factor. The xCT-based nomogram accurately predicted 1- and 3-year survival rates. Additionally, xCT knockout inhibited cell proliferation and enhanced chemoradiotherapy sensitivity in vitro and in vivo by promoting ferroptosis.Conclusion

High expression of xCT was associated with poor prognosis and chemoradiotherapy response in rectal cancer, representing a potential prognostic marker and therapeutic target.

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Cite

BibTeXRIS
BibTeX
@article{li2026high,
  title = {{High xCT expression indicates poor prognosis and chemoradiotherapy resistance in rectal cancer patients.}},
  author = {Yingru Li and Heng LiuFu and Zhilong Yuan and Wenchang Gan and Shaoyong Peng and Jinhong Li and Haiyang Xin and Canfeng Cai and Bing Zeng},
  journal = {Cancer cell international},
  year = {2026},
  month = jul,
  doi = {10.1186/s12935-026-04428-7},
  url = {https://europepmc.org/article/MED/42902388},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - High xCT expression indicates poor prognosis and chemoradiotherapy resistance in rectal cancer patients.
AU  - Yingru Li
AU  - Heng LiuFu
AU  - Zhilong Yuan
AU  - Wenchang Gan
AU  - Shaoyong Peng
AU  - Jinhong Li
AU  - Haiyang Xin
AU  - Canfeng Cai
AU  - Bing Zeng
PY  - 2026
DA  - 2026/07/01
JO  - Cancer cell international
DO  - 10.1186/s12935-026-04428-7
UR  - https://europepmc.org/article/MED/42902388
AB  - Background  xCT/SLC7A11, an amino acid transporter, is implicated in various cancers. However, its role in rectal cancer remains unclear. This study aimed to explore its predictive value for prognosis and chemoradiotherapy response in rectal cancer patients.Methods and materials  xCT expression was assessed using immunohistochemistry and RT-qPCR, and its associations with clinicopathological features and prognosis were analyzed. Single-cell RNA sequencing data and the TIMER platform were used to examine xCT's correlation with immune cell infiltration. A prognostic nomogram model was developed and evaluated with ROC, calibration, and decision curve analysis. Cell proliferation and cytotoxicity assays were conducted to assess xCT's role in ferroptosis and chemoradiotherapy sensitivity.Results  xCT expression was elevated in rectal cancer tissues and correlated with adverse clinicopathological features, including tumor regression grade (P < 0.001). Single-cell and immune infiltration analyses indicated that xCT was associated with the immune microenvironment. High xCT expression predicted worse overall and disease-free survival, and multivariate analysis confirmed it as an independent prognostic factor. The xCT-based nomogram accurately predicted 1- and 3-year survival rates. Additionally, xCT knockout inhibited cell proliferation and enhanced chemoradiotherapy sensitivity in vitro and in vivo by promoting ferroptosis.Conclusion  High expression of xCT was associated with poor prognosis and chemoradiotherapy response in rectal cancer, representing a potential prognostic marker and therapeutic target.
SN  - 1475-2867
ER  -