Blood drop detection of miRNAs can diagnose early lung cancer

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Blood drop detection of miRNAs can diagnose early lung cancer b

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Blood drop detection of miRNAs can diagnose early lung cancer before finding nodules丨2023 ASCO Highlights.

Lung cancer is one of the most common and deadliest malignancies globally. Screening and early diagnosis and treatment are effective measures to reduce the mortality rate of lung cancer in the general population.

The National Lung Screening Trial (NLST) conducted in the United States showed that annual low-dose computed tomography (LDCT) screening for high-risk individuals for three consecutive years can increase the detection rate of lung cancer by 13% and reduce the relative mortality rate by 20% (95% CI 6.8-26.7; P = 0.004). It also resulted in a 6.7% reduction in all-cause mortality (95% CI 1.2-13.6; P = 0.02) [1].

The criteria for including high-risk groups in the NLST trial are: aged 55-74 years, with a smoking history of at least 30 packs/year (and if quitting, the smoking cessation time is <15 years), and annual low-dose spiral CT screening is recommended for this group For non-high-risk groups, our current emphasis is to minimize unnecessary CT screening.

However, at least one quarter of lung cancer patients worldwide have never smoked, so many in the general population do not meet the criteria for lung cancer screening. In addition, due to various reasons such as limited screening criteria for LDCT population, low awareness, high false positive rate, and low LDCT screening cannot be widely and effectively implemented in countries around the world [2] .

Therefore, we still need to continue to consider the standards of lung cancer screening and explore detection methods that can perform early detection, predict metastasis and prognosis, and be less invasive, which play an important role in improving the survival rate of lung cancer patients. Blood testing is a recognized efficient and convenient way.

The 2023 American Society of Clinical Oncology (ASCO) Congress held in Chicago, USA from June 2 to June 6 published a poster study on “Early detection of lung cancer using small RNAs” (Abstract: 3035) [3] . So, can the “blood test for cancer” really become an effective means of clinically detecting lung cancer?

miRNA for early lung cancer detection

Research design

The study prospectively recruited 1,189 patients who met the 2013 USPSTF lung cancer screening criteria ( aged 55-80, smoked more than 30 packs per year and were still smoking or quit smoking for less than 15 years ), Stable whole blood was collected from the patient.

Ultra-deep sequencing of microRNAs (miRNAs) using methods that deplete highly abundant erythrocyte RNA extends bandwidth to detect less abundant species originating from plasma or immune cell compartments.

Using 100 random data splits to train and evaluate a logistic regression classifier using miRNA expression, 18 signatures (miLungs) of miRNA signature consistency were found and validated in an independent cohort (246 patients).

Research results

The study developed a diagnostic model and reported a median ROC AUC of 0.86 (95% CI 0.84-0.86) for the discovery cohort and an overall AUC of 0.84 for the validation cohort.

The diagnostic power of the miRNA assay improved from AUC 0.73 (95% CI 0.71-0.76) for stage I lung cancer to AUC 0.90 (95% CI 0.89-0.90) for stage IV lung cancer.

This suggests that miRNAs exhibit strong diagnostic potential, and the detection accuracy is much higher than that of existing conventional tumor markers.

Tumor shedding of the L1 stalk, plasma-bound ribosomal RNA fragments, was also found to be a major predictor of lung cancer.

Plasma-bound ribosomal RNA fragments are reduced following surgery for therapeutic purposes. In other experiments, dried blood point collection and sequencing revealed that microRNA analysis may be obtained through home sampling.

Table 1. Characteristics and conditions of patients enrolled in the study

Plasma miRNA has an 80% sensitivity for early detection of lung cancer before CT reveals imaging abnormalities

miRNA is a small non-coding RNA of 19-22 bases contained in body fluids such as blood, urine, and sputum, which can cause translation inhibition and/or mRNA degradation through complementary pairing with target mRNA sequences, and participate in cell proliferation, differentiation, and apoptosis.

Various pathophysiological processes such as death, body metabolism and tumor occurrence and development. Dysregulation of miRNA expression can be found in many malignant tumors including lung cancer.

A related previous study showed that a signature of 16 ratios consisting of 15 miRNAs could correctly discriminate 18 subjects in the training set who developed lung cancer (18/20, 90% sensitivity), and in 5 control Only 1 positive result in the pool (80% specificity).

In the validation dataset, miRNAs identified 12 of the 15 samples collected before spiral CT detection of lung cancer, with a sensitivity of 80% and a specificity of 90% (AUC-ROC = 0.85, P < 0.0001) [4 ] .

The predictive value of this signature was assessed useful 28 months before disease onset, and mir-660, mir-140-5p, mir451, mir-28-3p, mir-30c, and mir-92a were the most commonly dysregulated miRNA types.

A study by Bianchi et al. established a diagnostic model consisting of 34 serum miRNAs, and the scoring criteria using this model could identify patients with early non-small cell lung cancer (NSCLC) from asymptomatic high-risk groups with 80% accuracy, and could Accurately distinguish between benign and malignant [5] .

Figure 1. Analysis of miRNA expression in plasma samples collected before and during disease onset

miRNAs exist not only in lung cancer tissues, but also in blood circulation. More importantly, serum and plasma miRNAs can still be detected after high temperature, sudden cooling, different pH, and multiple freeze-thaws, especially can resist the degradation of RNase, which provides a basis for the detection and diagnosis of tumors by serum and plasma miRNAs [6] .

Compared with the existing lung cancer detection methods, miRNA has the advantages of less detection damage, good specificity, and high sensitivity. In the future, it has great potential to be applied to early lung cancer diagnosis, and even to judge the prognosis and metastasis of lung cancer.

Summary

The 2023 ASCO study concluded based on data that miRNA-based blood tests have the potential to replace LDCT screening in the future for early detection of smoking-related lung cancer .

At the same time, we also look forward to more in-depth studies with a larger sample size in the future to explore the relationship between miRNAs and the occurrence and development of lung cancer and other tumors, so as to provide more effective and convenient diagnostic methods for clinical practice.

references:

[1] B Milleron, et al. Lung screening. Rev Pneumol Clin . 2017 Feb;73(1):27-33.

[2] Carter-Bawa L, et al. Leveraging social media to increase lung cancer screening awareness, knowledge and uptake among high‑risk populations (The INSPIRE‑Lung Study): study protocol of design and methods of a community‑based randomized controlled trial. BMC Public Health. 2023 May 26;23(1):975.

[3] Early detection of lung cancer using small RNAs. 2023 ASCO Abstract 3035.

[4] Mattia Boeri, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci USA . 2011 Mar 1;108(9):3713-8.

[5] Bianchi F, Nicassio F, Marzi M, et al. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer［J］．EMBO Mol Med, 2011, 3(8): 495-503.

[6] Zheng Cuiling, Han Xiaohong. The role of microRNA in the diagnosis, targeted therapy and prognosis of lung cancer [J]. Chinese Journal of Laboratory Medicine, 2012, 35(6):3.

Blood drop detection of miRNAs can diagnose early lung cancer before finding nodules丨2023 ASCO Highlights.

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