摘要:
Background::Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [
EGFR]; anaplastic lymphoma kinase [
ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.
Methods::Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the
Kapp and
Dapp parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the
EGFR,
ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC,
Kapp,
Dapp) and pathologic outcomes (
EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.
Results::Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of
EGFR- and
ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The
Kapp values were significantly higher among patients with
EGFR-positive mutations (0.81 ± 0.12
vs. 0.66 ± 0.10,
t = 6.41,
P < 0.001),
ALK rearrangement-negative (0.76 ± 0.12
vs. 0.60 ± 0.15,
t = 4.09,
P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12
vs. 0.58 ± 0.13,
t = 4.88,
P < 0.001). The
Dapp values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm
2/ms
vs. 4.20 ± 0.83 μm
2/ms,
t = 4.80,
P < 0.001) and
EGFR-positive mutations (3.11 ± 0.73 μm
2/ms
vs. 3.59 ± 0.77 μm
2/ms,
t = 3.12,
P = 0.002). The differences in mean
Dapp (3.73 ± 1.26 μm
2/ms
vs. 3.26 ± 0.68 μm
2/ms,
t = 1.96,
P = 0.053) or ADC values ([1.34 ± 0.81] × 10
-3 mm
2/s
vs. [1.33 ± 0.41] × 10
-3 mm
2/s,
t = 0.07,
P = 0.941) between the groups with or without
ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with
EGFR-positive mutation ([1.19 ± 0.37] × 10
-3 mm
2/s
vs. [1.50 ± 0.53] × 10
-3 mm
2/s,
t = 3.38,
P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10
-3 mm
2/s
vs. [1.67 ± 0.77] × 10
-3 mm
2/s,
t = 2.88,
P = 0.005).
Kapp was strongly positively correlated with
EGFR mutations (
r = 0.844,
P = 0.008), strongly positively correlated with Ki-67 PI (
r = 0.882,
P = 0.001), and strongly negatively correlated with
ALK rearrangements (
r = -0.772,
P = 0.001).
Dapp was moderately correlated with
EGFR mutations (
r = -0.650,
P = 0.024) or Ki-67 PI (
r = -0.734,
P = 0.012). ADC was moderately correlated with Ki-67 PI (
r = -0.679,
P = 0.033).
Conclusions::The
Kapp value of DKI parameters was strongly correlated with different expression of
EGFR,
ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.