Evidence map›Paper›PMID 35397601›Full record

ArticleBMC cancer2022

High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy.

Fabio Walther, Jana Ladina Berther, Alexandros Lalos, Michaela Ramser, Simone Eichelberger, Robert Mechera, Savas Soysal, Simone Muenst, Alberto Posabella, Uwe Güth and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Fabio Walther *University Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Jana Ladina Berther *University Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Alexandros LalosUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Michaela RamserUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Simone EichelbergerUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Robert MecheraUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Savas SoysalUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Simone MuenstInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.
Alberto PosabellaUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Uwe GüthBrustzentrum Zürich, Seefeldstrasse 214, 8008, Zürich, Switzerland.
Sylvia StadlmannInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.
Luigi TerraccianoInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.
Raoul A DroeserUniversity Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland. RaoulAndre.Droeser@clarunis.ch.
Jasmin Zeindler *University Center for Gastrointestinal and Liver Diseases (Clarunis), University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
Gad Singer *Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.
University of Basel · CHUniversity Hospital of Basel · CHKantonsspital Baden · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOvarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS).

methodsA tissue microarray of 47 primary high grade ovarian serous carcinomas and their recurrences was stained with primary antibodies directed against CXCR4 and pCXCR4. Beside the evaluation of the absolute tumor as well as TIC expression in primary and recurrent cancer biopsies the corresponding ratios for pCXCR4 and CXCR4 were generated and analyzed. The clinical endpoints were response to chemotherapy, OS as well as RFS.

resultsPatients with a high pCXCR4/CXCR4 TIC ratio in primary cancer biopsies showed a significant longer RFS during the first two years (p = 0.025). However, this effect was lost in the long-term analysis including a follow-up period of 5 years (p = 0.128). Interestingly, the Multivariate Cox regression analysis showed that a high pCXCR4/CXCR4 TIC ratio in primary cancer independently predicts longer RFS (HR 0.33; 95CI 0.13 - 0.81; p = 0.015). Furthermore a high dichotomized distribution of CXCR4 positive tumor expression in recurrent cancer biopsies showed a significantly longer 6-month RFS rate (p = 0.018) in comparison to patients with low CXCR4 positive tumor expression. However, this effect was not independent of known risk factors in a Multivariate Cox regression (HR 0.57; 95CI 0.24 - 1.33; p = 0.193).

conclusionsTo the best of our knowledge we show for the first time that a high pCXCR4/CXCR4 TIC ratio in primary HGSOC biopsies is indicative for better RFS and response to chemotherapy. HIGHLIGHTS: • We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer.

Indexed as

Cystadenocarcinoma, SerousOvarian NeoplasmsReceptors, CXCR4FemaleHumansNeoplasm Recurrence, LocalPrognosisSignal TransductionCXCR4 protein, humanReceptors, CXCR4ChemokinesChemosensitivityCXCR4Ovarian cancerPCXCR4Prognostic significanceTumor expressionTumor infiltrating immune cells

Identifiers

PMID35397601
PMCPMC8994232
OpenAlexW4223534714

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.