PMID- 34976180 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220104 IS - 1837-9664 (Print) IS - 1837-9664 (Electronic) IS - 1837-9664 (Linking) VI - 13 IP - 1 DP - 2022 TI - Elevated CXCL12 in the plasma membrane of locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a potential prognostic marker. PG - 162-173 LID - 10.7150/jca.64082 [doi] AB - Background: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) has been shown to improve sphincter preservation and local pelvic control, but the efficacy of nCRT plateaus due to metastasis. CXC chemokine ligand 12 (CXCL12) has a critical impact on cancer development and metastasis. Methods: By investigating public databases containing LARC patient data, CXCL12, CXCR4 and FAPalpha expression was analyzed via the Tumor Immune Estimation Resource (TIMER) and GSEA. Immunohistochemistry was applied to a total of 121 surgically resected specimens consisting of 61 LARCs after nCRT and 60 LARCs with no nCRT and 16 cases with endoscopic resection of high-grade colorectal adenoma. Results: By investigating public databases containing LARC patient data, CXCL12 expression is correlated with poor prognosis, immune cell infiltration, epithelial- mesenchymal transition, and angiogenesis in LARC. Furthermore, radiation selectively induced CXCL12, CXCR4 and FAPalpha expression in tumor tissues. Immunohistochemistry results showed that the levels of CXCL12, CXCR4, and FAPalpha in LARC cells after nCRT were higher than in LARC cells untreated with nCRT (p < 0.001 for each). Elevated levels of CXCL12 in the plasma membrane of LARC cells after nCRT demonstrated an association with the period of freedom from recurrence (FFR) in univariate and multivariate survival analyses (p = 0.005 and p = 0.031, respectively). Conclusions: The expression of CXCL12 may influence the survival and invasive properties of LARC cells during nCRT and promote cancer recurrence. We suggest that CXCL12 expression in the plasma membrane of radioresistant LARC cells may be a predictive factor of recurrence and a viable therapeutic strategy to control radioresistant LARC recurrence. CI - (c) The author(s). FAU - Kim, Sup AU - Kim S AD - Department of Radiation Oncology, Chungnam National University School of Medicine, 288 Munhwa Street, Daejeon 35015, Korea. AD - Department of Radiation Oncology, Chungnam National University Hospital, 282 Munwha-ro, Daejeon 35015, Korea. FAU - Yeo, Min-Kyung AU - Yeo MK AD - Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea. AD - Department of Pathology, Chungnam National University Hospital, 282 Munwha-ro, Daejeon 35015, Korea. FAU - Kim, Jun-Sang AU - Kim JS AD - Department of Radiation Oncology, Chungnam National University School of Medicine, 288 Munhwa Street, Daejeon 35015, Korea. AD - Department of Radiation Oncology, Chungnam National University Hospital, 282 Munwha-ro, Daejeon 35015, Korea. FAU - Kim, Ji-Yeon AU - Kim JY AD - Department of Surgery, Division of Colorectal Surgery, Chungnam National University School of Medicine, Daejeon, Republic of Korea. FAU - Kim, Kyung-Hee AU - Kim KH AD - Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea. AD - Department of Pathology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong-si 30099, Korea. LA - eng PT - Journal Article DEP - 20220101 PL - Australia TA - J Cancer JT - Journal of Cancer JID - 101535920 PMC - PMC8692683 OTO - NOTNLM OT - CXCL12 OT - locally advanced rectal adenocarcinoma OT - neoadjuvant chemoradiotherapy OT - plasma membrane OT - recurrence COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2022/01/04 06:00 MHDA- 2022/01/04 06:01 PMCR- 2022/01/01 CRDT- 2022/01/03 05:40 PHST- 2021/06/20 00:00 [received] PHST- 2021/11/10 00:00 [accepted] PHST- 2022/01/03 05:40 [entrez] PHST- 2022/01/04 06:00 [pubmed] PHST- 2022/01/04 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - jcav13p0162 [pii] AID - 10.7150/jca.64082 [doi] PST - epublish SO - J Cancer. 2022 Jan 1;13(1):162-173. doi: 10.7150/jca.64082. eCollection 2022.