The clinicopathological and prognostic value of CXCR4 expression in patients with lung cancer: a meta-analysis

Qiu, Liping; Xu, Yanyan; Xu, Hongxing; Yu, Biyun

doi:10.1186/s12885-022-09756-1

Cited by 11 publications

(9 citation statements)

References 60 publications

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“…Moreover, the (quantified) intratumoral lesion variability among multiple observers was higher on FAPI-targeted PET/CT when compared with the present findings on SUV max for [ 68 Ga]pentixafor 35 . As a possible explanation, substantial and consistent CXCR4 upregulation has already been described in an ex vivo setting for both aggressive lung cancer and NEN 36,37 . As we also enrolled mainly those tumor types, those previous immunohistochemical findings may partially explain the high concordance rates of minimum 0.92 for TLs.…”

Section: Discussionsupporting

confidence: 65%

Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4–Directed Molecular Imaging and Therapy

et al. 2023

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BackgroundWe aimed to evaluate the interobserver agreement rates in patients scanned with C-X-C motif chemokine receptor 4 (CXCR4)–directed PET/CT, including the rate of patients eligible for CXCR4-targeted radioligand therapy (RLT) based on scan results.MethodsFour independent observers reviewed 50 CXCR4-targeted [68Ga]pentixafor PET/CT of patients with various solid cancers. On a visual level, the following items were assessed by each reader: overall scan impression, number of organ and lymph node (LN) metastases and number of affected organs and LN regions. For a quantitative investigation, readers had to choose a maximum of 3 target lesions, defined as largest in size and/or most intense uptake per organ compartment. Reference tissues were also quantified, including unaffected hepatic parenchyma and blood pool. Last, all observers had to decide whether patients were eligible for CXCR4-targeted RLT. Concordance rates were tested using intraclass correlation coefficients (ICCs). For interpretation, we applied the definition of Cicchetti (with 0.4–0.59 indicating fair; 0.6–0.74, good; 0.75–1, excellent agreement).ResultsOn a visual level, fair agreement was achieved for an overall scan impression (ICC, 0.58; 95% confidence interval, 0.45–0.71). Organ and LN involvement (ICC, ≥0.4) demonstrated fair, whereas CXCR4 density and number of LN and organ metastases showed good agreement rates (ICC, ≥0.65). Number of affected organs and affected LN areas, however, showed excellent concordance (ICC, ≥0.76). Quantification in LN and organ lesions also provided excellent agreement rates (ICC, ≥0.92), whereas quantified uptake in reference organs provided fair concordance (ICC, ≥0.54). Again, excellent agreement rates were observed when deciding on patients eligible for CXCR4-RLT (ICC, 0.91; 95% confidence interval, 0.85–0.95).ConclusionsIn patients scanned with CXCR4-targeted PET/CT, we observed fair to excellent agreement rates for both molecular imaging and therapy parameters, thereby favoring a more widespread adoption of [68Ga]pentixafor in the clinic.

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Section: Discussionsupporting

confidence: 65%

Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4–Directed Molecular Imaging and Therapy

et al. 2023

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“…It was reported that high CXCR4 expression corresponds to bad prognosis for breast ( 88 ), lung ( 90 ) and colorectal ( 118 ) cancers contradicting TCGA-based findings ( Figures 3B, C ). It was recently reported that in advanced CD8 negative thyroid cancer, high expression of CXCR4 and its ligand CXCL12 (SDF-1) correlates with bad prognosis, thus contradicting to TCGA data ( 89 ).…”

Section: Expression Of Molecules Involved In the Ctc Cluster Formatio...mentioning

confidence: 83%

“…It was reported that high CXCR4 expression corresponds to bad prognosis for breast (88), lung (90) and colorectal (118) cancers Mechanisms of circulating tumor cells (CTC) cluster formation and their properties. Highlighted in green, the process of CTC clusters formation; Tumor cells can separate from adjacent cells with more mobile mesenchymal cells at the leading edge of the invasion and cells with more epithelial properties behind (4, 5).…”

Section: Expression Of Molecules Involved In the Ctc Cluster Formatio...mentioning

confidence: 99%

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Rozenberg

Buzdin²,

Mohammad³

et al. 2023

Front. Immunol.

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Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

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“…Labeling of cysteine-free peptides (2,5,7,9) was performed in the presence of 10% ethanol at 95 °C for 30 min. The stock solutions of cysteine-bearing peptides (1,6,8) were prepared in dithiothreitol (DTT, 10 mM final concentration) and radiolabeling was also performed in the presence of 10% ethanol at 75 °C for 30 min. For quality control, an aliquot of 5 μL was withdrawn from the mother solution and diluted in 50 μL of calcium diethylenetriamine pentaacetate (Ca-DTPA) solution.…”

Section: ■ Conclusionmentioning

confidence: 99%

“…This compound is used to mobilize hematopoietic stem cells into the peripheral blood for autologous transplantation in cancer patients. Also, elevated CXCR4 expression has been associated with poor disease prognosis, , which suggests imaging and quantification of CXCR4 levels to be clinically relevant for the management of patients with CXCR4-expressing malignancies.…”

Section: Introductionmentioning

confidence: 99%

Development of a New Class of CXCR4-Targeting Radioligands Based on the Endogenous Antagonist EPI-X4 for Oncological Applications

et al. 2023

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The peptide fragment of human serum albumin that was identified as an inhibitor of C–X–C motif chemokine receptor 4 (CXCR4), termed EPI-X4, was investigated as a scaffold for the development of CXCR4-targeting radio-theragnostics. Derivatives of its truncated version JM#21 (ILRWSRKLPCVS) were conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and tested in Jurkat and Ghost-CXCR4 cells. Ligand-1, -2, -5, -6, -7, -8, and -9 were selected for radiolabeling. Molecular modeling indicated that 177Lu-DOTA incorporation C-terminally did not interfere with the CXCR4 binding. Lipophilicity, in vitro plasma stability, and cellular uptake hinted 177Lu-7 as superior. In Jurkat xenografts, all radioligands showed >90% washout from the body within an hour, with the exception of 177Lu-7 and 177Lu-9. 177Lu-7 demonstrated best CXCR4-tumor targeting. Ex vivo biodistribution and single-photon emission computed tomography (SPECT)/positron emission tomography (PET)/CT imaging of 177Lu-7/68Ga-7 showed the same distribution profile for both radioligands, characterized by very low uptake in all nontargeted organs except the kidneys. The data support the feasibility of CXCR4-targeting with EPI-X4-based radioligands and designate ligand-7 as a lead candidate for further optimization.

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The clinicopathological and prognostic value of CXCR4 expression in patients with lung cancer: a meta-analysis

Cited by 11 publications

References 60 publications

Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4–Directed Molecular Imaging and Therapy

Interobserver Agreement Rates on C-X-C Motif Chemokine Receptor 4–Directed Molecular Imaging and Therapy

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Development of a New Class of CXCR4-Targeting Radioligands Based on the Endogenous Antagonist EPI-X4 for Oncological Applications

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