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Differential expression of circulating serum miR-1249-3p, miR-3195, and miR-3692-3p in non-small cell lung cancer

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Abstract

Global deregulation in miRNA expression is a hallmark of cancer cell. An estimated 2300 mature miRNAs are encoded by human genome; role of many of which in carcinogenesis and as cancer biomarkers remains unexplored. In this study, we investigated the utility of miR-3692-3p, miR-3195, and miR-1249-3p as biomarkers in non-small cell lung cancer (NSCLC). For this prospective study, 115 subjects, including 75 NSCLC patients and 40 controls, were recruited. The expression of miR-3692-3p, miR-3195, and miR-1249-3p was checked using qRT-PCR. The miRNA expression was correlated with survival outcome and therapeutic response. There were no significant differences in the mean age of NSCLC patients and controls (56.2 and 55.3 years, respectively; p = 0.3242). Majority of NSCLC patients (67%) were smokers. We observed a significant upregulation of miR-3692-3p expression (p < 0.0001), while the expression of miR-3195 (p = 0.0017) and miR-1249-3p was significantly downregulated (p < 0.0001) in the serum of NSCLC patients as compared to controls. The expression of miR-1249-3p was significantly upregulated in lung adenocarcinoma versus lung squamous cell carcinoma (p = 0.0178). Interestingly, patients who responded to chemotherapy had higher expression of miR-1249-3p than non-responders (p = 0.0107). Moreover, patients with higher expression of miR-3195 had significantly longer overall survival (p = 0.0298). In multivariate analysis, miR-3195 emerged as independent prognostic factor for overall survival. We conclude that the miR-3195 may have prognostic significance, while miR-1249-3p may predict therapeutic response in NSCLC. Further studies are warranted to elucidate the role of these miRNAs in lung carcinogenesis and their utility as candidate cancer biomarkers.

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Abbreviations

NSCLC:

Non-small cell lung cancer

LUSC:

Lung squamous cell carcinoma

LUAD:

Lung adenocarcinoma

miRNA:

MicroRNA

RT:

Room temperature

qRT-PCR:

Reverse transcription quantitative polymerase chain reaction

OS:

Overall survival

PFS:

Progression-free survival

ROC:

Receiver operating characteristic

AUC:

Area under the curve

ECOG PS:

Eastern Cooperative Oncology Group performance status

BC:

Breast cancer

HCC:

Hepatocellular cancer

PC:

Prostate cancer

GC:

Gastric cancer

BCR:

Biochemical recurrence

ICOS:

Inducible T-cell co-stimulator

UTR:

Untranslated region

CRC:

Colorectal cancer

HBV:

Hepatitis virus B

SP:

Side population

HOXB8:

Homeobox 8

VEGFA:

Vascular endothelial growth factor A

HMGA2:

High-mobility group AT-hook 2

APC2:

Adenomatous polyposis coli 2

Gli1:

Glioma-associated oncogene 1

PTCH-1:

Patched-1

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Acknowledgements

The authors gratefully acknowledge the financial support from the Science and Engineering Research Board (SERB), Govt. of India, New Delhi (Grant no. SB/YS/LS-348/2013) and All India Institute of Medical Sciences, New Delhi (Grant no. A-516).

Funding

The authors gratefully acknowledge the financial support from the Science & Engineering Research Board (SERB), Govt. of India, New Delhi (Grant no. SB/YS/LS-348/2013) and All India Institute of Medical Sciences, New Delhi (Grant no. A-516).

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Authors and Affiliations

  1. Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, 110029, India

    Sachin Kumar, Surender K. Sharawat, Vikas Gaur, Prabhat Singh Malik & Monu Pandey

  2. Department of Pulmonary Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India

    Ashraf Ali, Anant Mohan & Randeep Guleria

  3. Department of Surgical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, 110029, India

    Sunil Kumar

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  1. Sachin Kumar
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Contributions

SK, VG, and MP performed all the laboratory work. SK and SKS analyzed and interpreted the experimental data. AS, PSM, SK, AM and RG collected, analyzed, and interpreted the clinical data. SK designed the study and wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sachin Kumar.

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The authors declare that they have no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by ethics committee of All India Institute of Medical Sciences, New Delhi (Ref. No. IEC-155/07.04.2017, RP-13/2017). This article does not contain any studies with animals performed by any of the authors.

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Kumar, S., Sharawat, S.K., Ali, A. et al. Differential expression of circulating serum miR-1249-3p, miR-3195, and miR-3692-3p in non-small cell lung cancer. Human Cell 33, 839–849 (2020). https://doi.org/10.1007/s13577-020-00351-9

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