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High prevalence of CD44 and its ligand low molecular weight hyaluronan in plasma of HNSCC patients: clinical significance

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Abstract

Background

This study aims to evaluate the role of cancer stem cell marker, CD44, and its ligand HA as potential molecular biomarker for early detection of HNSCC.

Methods and results

The expression profile (mRNA/Protein) of CD44 variants were analysed in primary HNSCC lesions and plasma of the patients. Then, prevalence of HA variants was analysed in plasma of the patients. The mRNA expression of CD44 variants, CD44S and CD44v3, were significantly high in both early (stage I/II) and late (stage III/IV) invasive lesions, with predominant expression of CD44v3 in the late-stage lesions. In plasma of HNSCC patients, increased levels of SolCD44, CD44-ICD and unique 62 KD CD44 variants with respect to standard CD44S were seen, in comparison to their prevalence in plasma of normal individuals. The abundance of CD44-ICD and 62 KD variants were significantly high in plasma of late stage HNSCC patients. Interestingly, significantly high level of low molecular weight HA(LMW HA) with respect to high molecular weight HA(HMW HA) was seen in plasma of HNSCC patients irrespective of clinical stages. On the contrary, high HMW HA level in plasma of normal individuals was seen. The high level of LMW HA in plasma of HNSCC patients might be due to combinatorial effect of increased mRNA expression of HA synthesizing enzyme HAS1/2/3 and HA degrading enzyme HYAL1/2, as seen in the primary HNSCC samples.

Conclusion

Thus, our data revealed the importance of specific CD44 and HA variants in plasma of HNSCC patients during its development as potential non-invasive molecular biomarker of the disease.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

CSC:

Cancer stem cells

HNSCC:

Head and neck squamous cell carcinoma

CD44:

Cluster of differentiation 44

CD44-ICD:

CD44 inter-cytoplasmic domain

SolCD44:

Soluble CD44

HA:

Hyaluronic acid or Hyaluronan

LMW HA:

Low molecular weight HA

HMW HA:

High molecular weight HA

HAS:

HA synthase

HYAL:

Hyaluronidase

CTC:

Circulating tumor cell

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Acknowledgements

Financial support for this study was provided by extramural project from Indian Council of Medical Research (ICMR), Government of India (ICMR Grant No. 5/13/25/2019/NCD-III) awarded to S.D. and Fellowship to R.R. This study is also supported by extramural project from International Agency for Research on Cancer, France (IARC Return Grant, No. CRA/ETR/2019/1), awarded to S.D. with fellowship to N.C., and from NASI Senior Scientist Platinum Jubilee Fellowship (2020) awarded to Dr. C.K.P., and by extramural project grant by Indian Council of Medical Research, Government of India to Dr B.C. This study was also supported by CSIR-JRF/NET grant [Ref No. 09/030(0083)/2019-EMR-I] to F.S. from Council of Scientific & Industrial Research (CSIR), Government of India and institutional fellowship grant, to M.S.K., from Chittaranjan National Cancer Institute, Government of India.

Funding

This study was funded by Indian Council of Medical Research (5/13/25/2019/NCD‐III, Extramural Grant); Centre International de Recherche sur le Cancer (CRA/ETR/2019/1); Chittaranjan National Cancer Institute (Institutional JRF Fellowship); CSIR-JRF/NET grant (09/030(0083)/2019-EMR-I); National Academy of Sciences, india (NASI Senior Scientist Platinum Jubilee Fellowship).

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Authors and Affiliations

  1. Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Rituparna Roy, Nilanjana Chatterjee, Md Sadi Khan, Farhin Sultana, Bishnu Pada Chatterjee, Chinmay Kumar Panda & Sankhadeep Dutta

  2. Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Arindam Roy, Sagar Sen & Jayanta Chakrabarti

  3. Department of Head and Neck Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Sukanya Naskar & Rajdeep Guha

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  1. Rituparna Roy
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Contributions

Conceptualization of the study by SD and CKP. Methodology by RR. Formal analysis and investigation by RR, NC, FS, MSK. Sample acquisition by AR, SN, RG and SS. Writing—original draft preparation by RR, CKP and SD. Writing—review and editing by RR, CKP, BC and SD. Funding acquisition by SD, CKP, and BC. Resource support provided by JC and SD. Overall supervision by SD. The manuscript has been read and approved by all the authors.

Corresponding authors

Correspondence to Chinmay Kumar Panda or Sankhadeep Dutta.

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Conflict of interest

The authors have not disclosed any competing interests.

Ethical approval

All the participants were between 20 and 70 years of age and each of them gave a written informed consent before sample collection. This study was approved by the Ethical Committee of Chittaranjan National Cancer Institute [Ref No: CNCI-IEC‐SD‐2019‐8 dated 22.05.2019] and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Supplementary Information

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11033_2023_8950_MOESM1_ESM.jpg

Sample utilisation flowchart. Flowchart showing the use of different samples in different experiments during the study. Supplementary material 1 (JPG 1262.7 kb)

11033_2023_8950_MOESM2_ESM.jpg

Individual mRNA expression profile of CD44v. Heatmap showing the individual mRNA expression of CD44S and CD44v3 of the HNSCC patients. The left side panel shows the IDs for respective individuals, as given in Supplementary Table 1, here, N = normal, E = early and L = late stage samples. Supplementary material 2 (JPG 1235.7 kb)

11033_2023_8950_MOESM3_ESM.jpeg

Individual relative expression profile of CD44v. Heatmap showing the individual relative expression of different CD44 protein variants (SolCD44, CD44-ICD and unique 64 KD CD44 form) in comparison to the standard CD44, CD44S, in the plasma of the subjects. The left side panel shows the IDs for respective individuals, as given in Supplementary Table 1, here, N = normal, E = early stage (I/II) samples and L = late stage (III/IV) samples. Supplementary material 3 (JPEG 1232.4 kb)

11033_2023_8950_MOESM4_ESM.jpg

Individual prevalence of HA. Graph showing HA profile on individual basis and stagewise in the plasma samples. Supplementary material 4 (JPG 773.5 kb)

Supplementary material 5 (JPEG 1037.7 kb)

Supplementary material 6 (DOCX 66.9 kb)

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Roy, R., Chatterjee, N., Khan, M.S. et al. High prevalence of CD44 and its ligand low molecular weight hyaluronan in plasma of HNSCC patients: clinical significance. Mol Biol Rep 51, 157 (2024). https://doi.org/10.1007/s11033-023-08950-z

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