Open AccessComprehensive expressional analysis of chemosensitivity‐related markers in large cell neuroendocrine carcinoma of the lung
Author(s) -
Ohtaki Yoichi,
Kaira Kyoichi,
Yajima Toshiki,
ErkhemOchir Bilguun,
Kawashima Osamu,
Kamiyoshihara Mitsuhiro,
Igai Hitoshi,
Onozato Ryoichi,
Ibe Takashi,
Kosaka Takayuki,
Nakazawa Seshiru,
Nagashima Toshiteru,
Oyama Tetsunari,
Shirabe Ken
Publication year - 2021
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.14102
Subject(s) - medicine , chemotherapy , oncology , lung cancer , pathological , thymidylate synthase , univariate analysis , small cell lung carcinoma , immunohistochemistry , cancer research , pathology , multivariate analysis , small cell carcinoma , fluorouracil
Abstract Objectives Various drug‐sensitivity markers have been reported to be associated with tumor progression and chemotherapy resistance. Detailed expression profiles of sensitivity markers for cytotoxic chemotherapy in pulmonary large cell neuroendocrine carcinoma (LCNEC) remain unclear. Herein, we aimed to clarify the correlation between the expression of drug‐sensitivity markers and clinicopathological features, prognostic impact, and status of tumor immunity in patients with LCNEC. Methods We retrospectively analyzed the correlation between clinicopathological features and the expression of drug‐sensitivity‐related markers, including vascular endothelial growth factor 2 (VEGFR2), thymidylate synthase (TS), tubulin beta 3 class III (TUBB3), topoisomerase I (Topo‐I), and Topo‐II in 92 surgically resected LCNEC samples. Furthermore, we examined the prognostic significance of expression of these and their correlation with the immune cell status. Results Overall, high expression of TS, TUBB3, VEGFR2, Topo‐I, and Topo‐II was detected in 50 (54%), 31 (34%), 23 (25%), 65 (71%), and 36 (39%) samples, respectively. Univariate and multivariate analyses revealed that advanced pathological T and N factors, positive lymphatic permeation, and Topo‐II expression were independent unfavorable prognosticators for recurrence‐free survival, and advanced pathological T and N factors, Topo‐II positive expression, and TS positive expression were independent unfavorable prognosticators for overall survival. In terms of correlation with immune cell status, higher expression of VEGFR2 was closely linked to negative PD‐L1 expression. Conclusions These findings suggest that elevated Topo‐II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC.