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. 2024 Aug 31;13(8):1768-1779.
doi: 10.21037/tlcr-24-317. Epub 2024 Aug 17.

Redefining YAP1 in small cell lung cancer: shifting from a dominant subtype marker to a favorable prognostic indicator

Se-Il Go #  1 , Jung Wook Yang #  2 , Eun Jeong Jeong  3 , Woo Je Lee  3 , Sungwoo Park  3 , Dae Hyun Song  4 , Gyeong-Won Lee  3
Affiliations

Redefining YAP1 in small cell lung cancer: shifting from a dominant subtype marker to a favorable prognostic indicator

Se-Il Go et al. Transl Lung Cancer Res. .

Abstract

Background: Molecular and transcription factor subtyping were recently introduced to identify patients with unique clinical features in small cell lung cancer (SCLC). However, its prognostic relevance is yet to be established. This study aims to investigate the clinical implications and prognostic significance of transcription factor subtyping in SCLC using immunohistochemistry.

Methods: One hundred and ninety consecutive SCLC patients treated with platinum-based chemotherapy at a single institution were retrospectively reviewed. Expression of ASCL1, NeuroD1, POU2F3, and YAP1 was assessed by immunohistochemical staining and applied to determine the transcription factor subtype of each case.

Results: The association among transcription factors was not entirely mutually exclusive. YAP1 expression was the most significant prognostic indicator compared with other transcription factors or their related subtypes. Among patients with limited-stage disease (LD), complete response (CR) rates were 46.2% and 22.4% in the YAP1-positive and YAP1-negative groups, respectively. The median duration of response among patients who achieved CR was 64.8 and 36.4 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.06). Median overall survival (OS) in LD was 35.6 and 16.9 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.03). In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03).

Conclusions: Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD.

Keywords: Small cell lung cancer (SCLC); YAP1 protein; immunohistochemistry (IHC); molecular subtyping; transcription factors.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-317/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Representative images of immunohistochemical staining for transcription factors across their subtypes. Each image includes a scale bar representing 50 µm. QN, quadruple-negative.
Figure 2
Figure 2
Transcription factor expression and categorization across subtypes. (A) Heatmap visualization showing expression levels of transcription factors across different subtypes. H-scores (0–300) indicate the expression level, with color intensity corresponding to H-score values. (B,C) Sankey diagrams categorize expression levels of transcription factors as (B) high vs. low or negative and (C) positive vs. negative, showing their distribution across subtypes. A, ASCL1; N, NeuroD1; P, POU2F3; Y, YAP1; QN, quadruple-negative; (+), positive; (−), negative.
Figure 3
Figure 3
Overall survival is based on expression levels of transcription factors. (A-D) Overall survival based on a binary expression classification (negative or positive) of transcription factors. (E-H) Overall survival according to transcription factors’ negative, low, and high expression categories.
Figure 4
Figure 4
Kaplan-Meier survival curves by YAP1 expression. Progression-free survival (A,C) and overall survival (B,D) in limited- and extensive-stage, respectively.
See this image and copyright information in PMC

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