Long Distance From Microvessel to Cancer Cell Predicts Poor Prognosis in Non-Small Cell Lung Cancer Patients

Haiying Ding; Jiao Sun; Yu Song; Wenxiu Xin; Junfeng Zhu; Like Zhong; Yinbo Chen; Yiwen Zhang; Yinghui Tong; Luo Fang

doi:10.3389/fonc.2021.632352

Long Distance From Microvessel to Cancer Cell Predicts Poor Prognosis in Non-Small Cell Lung Cancer Patients

Front Oncol. 2021 Jun 11:11:632352. doi: 10.3389/fonc.2021.632352. eCollection 2021.

Authors

Haiying Ding¹, Jiao Sun¹, Yu Song¹, Wenxiu Xin¹, Junfeng Zhu¹, Like Zhong¹, Yinbo Chen², Yiwen Zhang³, Yinghui Tong¹, Luo Fang¹

Affiliations

¹ Department of Pharmacy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
² Department of Colorectal Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
³ Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Abstract

Background: Blood supply, which is crucial for nutrition and drug delivery, was determined by microvessel density as well as the diffusion distance between vessels and cancer cells. Therefore, we evaluated the distance from microvessels to cancer cells (D_mvcc) and its role in the prognosis of non-small cell lung cancer (NSCLC) patients.

Methods: Patients with primary NSCLC were retrospectively analyzed. The tumor samples were immunochemically stained with CD31 to visualize the microvessels. The D_mvcc was defined as the mean distance from each microvessel to its nearest cancer cell in the "hot-spot" of an individual patient. The patients were stratified into short- and long-distance groups using five strategies, including dichotomy by the median value, optimal cutoff, trichotomy, quartation and per-10 µm increase. The correlation between the D_mvcc and survival was evaluated by using univariate and multivariate analyses with various D_mvcc strategies.

Results: In total, 100 patients were analyzed. The median value of D_mvcc was 13.1 μm (ranged, 1.6 to 269.7 μm; mean value, 24.4 ± 33.5 μm). The optimal cutoff value of D_mvcc for predicting survival outcome was 20 μm. D_mvcc was significantly related to overall survival (OS) with all the five categories (p = 0.001-0.000004) and progression-free survival (PFS) categorized by optimal cutoff value (p = 0.024), trichotomy (p = 0.041) and per-10 µm increase (p = 0.040) after adjusting for other factors. Patients with longer D_mvcc (≥20 μm) were observed to have poor survival outcomes (OS: HR = 13.5, 95CI: 4.42-41.18, p = 0.000005; PFS: 3.26, 95CI: 1.56-6.81, p = 0.002). A high D_mvcc per-10 µm was associated with a significantly increased risk of cancer-related death and progression by 98% (p = 0.0001) and 30% (p = 0.044), respectively.

Conclusion: The NSCLC tissues had varying distances from microvessels to cancer cells, and long distances were strongly associated with poor survival.

Keywords: distance from microvessel to cancer cell; non-small cell lung cancer; overall survival; prognosis marker; progression free survival.