Characteristics and response to next‐generation sequencing‐guided therapy in locally advanced or metastatic esophageal cancer

Ma, Yuyan; Li, Wenjie; Chen, Shiyu; Lin, Shuimiao; Ding, Sijie; Zhou, Xiaomei; Liu, Tongxin; Wang, Rong; Wang, Wei

doi:10.1002/ijc.34315

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…TP53 is linked to a poorer outcome in ESCA. Patients with TTN, MUC16 mutations have a higher tumor mutation load and may benefit from immunotherapy ( 33 – 35 ). As a result, patients with a high level of CDKL3 expression may benefit less from immunotherapy and result in a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

Bi,

Liu,

Qin

et al. 2024

Front. Immunol.

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BackgroundCDKL3 has been associated with the prognosis of several tumors. However, the potential role of CDKL3 in immunotherapy and the tumor microenvironment (TME) in esophageal carcinoma (ESCA) remains unclear.MethodsIn this study, Cox regression analysis was used to assess the predictive value of CDKL3 for ESCA outcomes. We systematically correlated CDKL3 with immunological features in the TME. The role of CDKL3 in predicting the efficacy of immunotherapy was also analyzed. Correlation analysis, Cox analysis and LASSO Cox regression were used to construct the CDKL3-related autophagy (CrA) risk score model. The relationship between CDKL3 expression and postoperative pathological complete response (pCR) rate in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemoradiotherapy (nCRT) was evaluated using Immunohistochemical staining (IHC). The relationship between CDKL3 expression and autophagy induction was confirmed by immunofluorescence staining and western blot, and the effect of CDKL3 expression on macrophage polarization was verified by flow cytometry.ResultsHigh expression of CDKL3 was found in ESCA and was associated with poor prognosis in ESCA. Moreover, CDKL3 expression was negatively correlated with tumor-infiltrating immune cells (TIICs), the integrality of the cancer immunity cycles, and anti-tumor signatures, while CDKL3 expression was positively correlated with suppressive TME-related chemokines and receptors, immune hyperprogressive genes, and suppressive immune checkpoint, resulting in immunosuppressive TME formation in ESCA. An analysis of immunotherapy cohorts of the ESCA and pan-cancer showed a better response to immunotherapy in tumor patients with lower CDKL3 levels. The CrA risk score model was constructed and validated to accurately predict the prognosis of ESCA. Notably, the CrA risk score of ESCA patients was significantly positively correlated with M2 macrophages. Furthermore, knockdown CDKL3 in KYSE150 cells could inhibit autophagy induction and M2 macrophage polarization. And, radiation could downregulate CDKL3 expression and autophagy induction, while ESCC patients with high CDKL3 expression had a significantly lower response rate after nCRT than those with low CDKL3 expression.ConclusionCDKL3 may play an important role in anti-tumor immunity by regulating autophagy to promote the formation of immunosuppressive TME, thus playing a critical role in the prognosis of ESCA.

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Section: Discussionmentioning

confidence: 99%

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

Bi,

Liu,

Qin

et al. 2024

Front. Immunol.

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“…This study resulted in the identification of 227 mutated genes. Among them, XRCC1 exhibited a substantial number of mutations and was associated with autophagy [ 106 ]. Demirbag-Sarikaya et al observed that the autophagy-related molecule autophagy-related protein 5 (ATG5) interacts with both XRCC5 and XRCC6.…”

Section: Role Of Xrcc In Autophagymentioning

confidence: 99%

X-ray cross-complementing family: the bridge linking DNA damage repair and cancer

Liu,

Peng,

Zhang

et al. 2023

J Transl Med

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Genomic instability is a common hallmark of human tumours. As a carrier of genetic information, DNA is constantly threatened by various damaging factors that, if not repaired in time, can affect the transmission of genetic information and lead to cellular carcinogenesis. In response to these threats, cells have evolved a range of DNA damage response mechanisms, including DNA damage repair, to maintain genomic stability. The X-ray repair cross-complementary gene family (XRCC) comprises an important class of DNA damage repair genes that encode proteins that play important roles in DNA single-strand breakage and DNA base damage repair. The dysfunction of the XRCC gene family is associated with the development of various tumours. In the context of tumours, mutations in XRCC and its aberrant expression, result in abnormal DNA damage repair, thus contributing to the malignant progression of tumour cells. In this review, we summarise the significant roles played by XRCC in diverse tumour types. In addition, we discuss the correlation between the XRCC family members and tumour therapeutic sensitivity.

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Genetic testing of neoadjuvant therapy patients with esophageal cancer

Huang,

Xu,

et al. 2024

Gene Reports

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Characteristics and response to next‐generation sequencing‐guided therapy in locally advanced or metastatic esophageal cancer

Cited by 3 publications

References 45 publications

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

CDKL3 shapes immunosuppressive tumor microenvironment and initiates autophagy in esophageal cancer

X-ray cross-complementing family: the bridge linking DNA damage repair and cancer

Genetic testing of neoadjuvant therapy patients with esophageal cancer

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