Dissecting the single-cell transcriptome network in patients with esophageal squamous cell carcinoma receiving operative paclitaxel plus platinum chemotherapy

Zhencong Chen; Yiwei Huang; Zhengyang Hu; Mengnan Zhao; Yunyi Bian; Zongwei Chen; Yuansheng Zheng; Guoshu Bi; Yanrui Pang; Cheng Zhan; Zongwu Lin; Weigang Guo; Qun Wang; Lijie Tan

doi:10.1038/s41389-021-00359-2

Dissecting the single-cell transcriptome network in patients with esophageal squamous cell carcinoma receiving operative paclitaxel plus platinum chemotherapy

Oncogenesis. 2021 Oct 26;10(10):71. doi: 10.1038/s41389-021-00359-2.

Authors

Zhencong Chen^#¹, Yiwei Huang^#¹, Zhengyang Hu^#¹, Mengnan Zhao^#¹, Yunyi Bian¹, Zongwei Chen¹, Yuansheng Zheng¹, Guoshu Bi¹, Yanrui Pang², Cheng Zhan³, Zongwu Lin⁴, Weigang Guo⁵, Qun Wang¹, Lijie Tan¹

Affiliations

¹ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, 200032, Shanghai, China.
² Department of Pathology, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, 200032, Shanghai, China.
³ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, 200032, Shanghai, China. czhan10@fudan.edu.cn.
⁴ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, 200032, Shanghai, China. lin.zongwu@zs-hospital.sh.cn.
⁵ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, 200032, Shanghai, China. guo.weigang@zs-hospital.sh.cn.

^# Contributed equally.

Abstract

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of all cases of esophageal cancers worldwide. Although neoadjuvant chemotherapy (NACT-ESCC) improves the survival of ESCC patients, the five-year survival rate of these patients is dismal. The tumor microenvironment (TME) and tumor heterogeneity decrease the efficacy of ESCC therapy. In our study, 113,581 cells obtained from five ESCC patients who underwent surgery alone (SA-ESCC) and five patients who underwent preoperative paclitaxel plus platinum chemotherapy (NACT-ESCC), were used for scRNA-seq analysis to explore molecular and cellular reprogramming patterns. The results showed samples from NACT-ESCC patients exhibited the characteristics of malignant cells and TME unlike samples from SA-ESCC patients. Cancer cells from NACT-ESCC samples were mainly at the 'intermediate transient stage'. Stromal cell dynamics showed molecular and functional shifts that formed the immune-activation microenvironment. APOE, APOC1, and SPP1 were highly expressed in tumor-associated macrophages resulting in anti-inflammatory macrophage phenotypes. Levels of CD8+ T cells between SA-ESCC and NACT-ESCC tissues were significantly different. Immune checkpoints analysis revealed that LAG3 is a potential immunotherapeutic target for both NACT-ESCC and SA-ESCC patients. Cell-cell interactions analysis showed the complex cell-cell communication networks in the TME. In summary, our findings elucidate on the molecular and cellular reprogramming of NACT-ESCC and ESCC patients. These findings provide information on the potential diagnostic and therapeutic targets for ESCC patients.