Niu YX, Hu M, Zhao WF, Yang HJ. Expression of stem cell marker musashi-1 and its relationship with survival prognosis in patients with resectable esophageal squamous cell carcinoma. World J Stem Cells 2025; 17(8): 107013 [DOI: 10.4252/wjsc.v17.i8.107013]
Corresponding Author of This Article
Ya-Xuan Niu, Technician in Charge, Department of Laboratory, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Zhengzhou 450000, Henan Province, China. mini209@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ya-Xuan Niu, Min Hu, Department of Laboratory, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450000, Henan Province, China
Wei-Feng Zhao, Hong-Jie Yang, Tumor Center, Henan Provincial People’s Hospital, Zhengzhou 450000, Henan Province, China
Author contributions: Niu YX designed the study; Hu M performed the experiments; Zhao WF and Yang HJ analysed the data; Niu YX, Hu M, Zhao WF, and Yang HJ contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Henan Provincial People’s Hospital (Approval No. HXDXB24011), and the study followed the ethical guidelines of the Declaration of Helsinki.
Informed consent statement: Informed consent was obtained from all study participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ya-Xuan Niu, Technician in Charge, Department of Laboratory, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Zhengzhou 450000, Henan Province, China. mini209@126.com
Received: March 14, 2025 Revised: April 19, 2025 Accepted: July 11, 2025 Published online: August 26, 2025 Processing time: 161 Days and 0.5 Hours
Abstract
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors globally, with its incidence particularly high in East Asia.
AIM
To analyze the expression of the stem cell marker musashi-1 in patients with resectable ESCC undergoing neoadjuvant chemotherapy and its relationship with patient survival prognosis.
METHODS
A retrospective analysis was conducted on the clinical data of 74 ESCC patients treated at our hospital from June 2020 to January 2022. All patients received neoadjuvant chemotherapy and surgical resection. Immunohistochemistry (IHC) was used to detect musashi-1 expression in tumor tissues. Based on the expression intensity, patients were divided into group A (n = 30, IHC total score > 2 indicating high expression) and group B (n = 44, IHC total score 0-2 indicating low expression). The clinical pathological differences between groups A and B were compared. The treatment outcomes of both groups were compared. Univariate and multivariate Cox regression analysis was performed to identify factors affecting patient prognosis. Kaplan-Meier survival analysis was used, and log-rank tests were conducted to compare differences between groups.
RESULTS
There were statistically significant differences in tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, lymphovascular invasion, and intraoperative blood loss between groups A and B (P < 0.05). The disease control rate in group A (86.67%) was lower than that in group B (100.00%) (χ2 = 3.868, P = 0.049); the objective response rate in group A (33.33%) was lower than that in group B (70.45%) (χ2 = 9.948, P = 0.001). The proportion of tumor regression grade 3 + 4 + 5 grades in group A (80.00%) was higher than in group B (43.18%) (χ2 = 9.933, P = 0.001). Univariate analysis showed that tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, and musashi-1 expression were associated with patient prognosis (P < 0.05). Cox regression analysis model. The results indicated that T stage [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 2.14-7.37], N stage (HR = 1.70, 95%CI: 1.12-2.36), clinical stage (HR = 2.08, 95%CI: 1.36-3.85), pathological grade (HR = 1.54, 95%CI: 1.07-2.41), and musashi-1 expression (HR = 2.72, 95%CI: 2.03-4.11) were independent risk factors affecting patient prognosis (P < 0.05). Kaplan-Meier survival curves showed that the median overall survival in group A was 17 months, while in group B it was 28 months. Log-rank analysis revealed that the overall survival rate in group A was worse than in group B (χ2 = 2.635, P = 0.033).
CONCLUSION
The expression of musashi-1 is closely related to the treatment efficacy, prognosis, and survival of ESCC patients. It is expected to be a potential biomarker for evaluating the efficacy and survival prognosis of ESCC patients.
Core Tip: The expression level of musashi-1 has been found to be closely associated with the treatment efficacy, disease progression, and overall survival of patients with esophageal squamous cell carcinoma. As a key regulator involved in tumorigenesis and cancer stem cell maintenance, musashi-1 holds promise as a novel biomarker for predicting therapeutic response and assessing long-term prognosis in esophageal squamous cell carcinoma patients, potentially guiding personalized treatment strategies.
Citation: Niu YX, Hu M, Zhao WF, Yang HJ. Expression of stem cell marker musashi-1 and its relationship with survival prognosis in patients with resectable esophageal squamous cell carcinoma. World J Stem Cells 2025; 17(8): 107013
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors globally, with its incidence particularly high in East Asia[1,2]. Despite significant advances in diagnostic technology and treatment strategies in recent years, the overall prognosis for ESCC patients remains poor, with a 5-year survival rate of only 15%-25%[3]. This is mainly due to the lack of obvious early symptoms, with most patients being diagnosed at advanced stages, thus missing the optimal treatment window[4]. Therefore, exploring effective early diagnostic biomarkers and personalized treatment strategies is of great significance for improving the prognosis of ESCC patients. Neoadjuvant chemotherapy (NCT) is one of the standard treatment modalities for resectable ESCC patients and has been proven by numerous clinical studies[5,6] to significantly reduce tumor size, lower clinical staging, and increase surgical resectability. Furthermore, NCT can reduce the risk of postoperative recurrence and metastasis by eliminating micrometastases[7]. However, despite significant efficacy in some patients, there is considerable heterogeneity in the response to chemotherapy, which may be closely related to the molecular characteristics of the tumor, the tumor microenvironment, and the presence of cancer stem cells (CSCs). CSCs are a small subpopulation of tumor cells with the ability to self-renew, differentiate into multiple lineages, and exhibit high tumorigenicity. Studies have shown that CSCs play a key role in tumor initiation, progression, metastasis, and drug resistance[8,9]. Not only can they maintain tumor growth through self-renewal, but they also promote tumor invasion and metastasis by producing heterogeneous tumor cell populations via differentiation. Moreover, CSCs are naturally resistant to conventional chemotherapy and radiotherapy, which is believed to be one of the main reasons for tumor recurrence and treatment failure[10]. Therefore, research targeting CSCs has become a hot topic in cancer therapy. Musashi-1 is a highly conserved RNA-binding protein, first identified in fruit flies, named for its crucial role in nervous system development[11]. Recently, musashi-1 has been shown to be highly expressed in various normal stem cells and CSCs, where it regulates self-renewal and differentiation. In several malignant tumors, high expression of musashi-1 has been closely associated with tumor invasiveness, metastasis, and poor prognosis[12,13]. Studies have demonstrated that musashi-1 promotes self-renewal and drug resistance in CSCs by regulating the expression of downstream target genes (such as Notch, Wnt, and mammalian target of rapamycin signaling pathways), thereby driving tumor progression and recurrence[14]. However, the expression of musashi-1 in ESCC and its relationship with NCT efficacy and patient prognosis have not yet been fully elucidated. Therefore, this study retrospectively analyzed the clinical data of resectable ESCC patients to explore the expression of musashi-1 in tumor tissues and its relationship with clinical pathological features, NCT efficacy, and patient survival prognosis. The aim was to provide theoretical guidance for personalized treatment of ESCC patients and lay the foundation for developing novel therapeutic strategies targeting CSCs.
In addition, although the focus of this study remains on the efficacy analysis of NCT, the potential role of musashi-1 in tumor immune evasion is also worth attention, considering the significance of immunotherapy in metastatic ESCC. In recent years, the widespread application of immune checkpoint inhibitors has significantly changed the treatment landscape of esophageal cancer. As a marker of CSCs, musashi-1 may play an important role in tumor immune evasion and immune tolerance[15]. In the future, exploring the potential of combining musashi-1 with immunotherapy may provide new treatment directions for esophageal cancer patients.
MATERIALS AND METHODS
Study subjects
A retrospective analysis was conducted on the clinical data of 74 ESCC patients admitted to our hospital between June 2020 and January 2022. All patients received NCT and surgical resection treatment in our hospital. Inclusion criteria: (1) Histopathological diagnosis of ESCC; (2) Clinical staging based on the 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system[16], with stages T2-4a, N0-2, and M0 for resectable ESCC patients; (3) All patients received NCT treatment in our hospital, followed by radical surgical resection after NCT completion, aged 18-75 years, and confirmed to tolerate NCT and surgical treatment by the Eastern Cooperative Oncology Group performance status[17] and laboratory tests; and (4) Complete and accurate clinical pathological data, treatment records, and follow-up information available for analysis. Exclusion criteria: (1) Patients with a history of or concurrent malignant tumors; (2) Patients who received prior radiotherapy, targeted therapy, or immunotherapy before NCT; (3) Imaging examination [e.g., computed tomography (CT), positron emission tomography-CT] indicating distant metastasis (M1); (4) Patients with severe heart, lung, liver, kidney failure, or other systemic diseases that could not tolerate NCT or surgical treatment; (5) Pregnant or lactating women; (6) Patients with active infection or inflammatory conditions; and (7) Patients with poor compliance who were unable to complete treatment and follow-up as required by the study. Immunohistochemistry (IHC) was used to detect the expression of musashi-1 in tumor tissues, and based on the expression intensity, patients were divided into group A (n = 30, IHC total score > 2, categorized as high expression) and group B (n = 44, IHC total score 0-2, categorized as low expression). This study was approved by the Medical Ethics Committee (Approval No. HXDXB24011), and the study followed the ethical guidelines of the Declaration of Helsinki.
IHC detection of musashi-1
To assess the expression of musashi-1 in ESCC tissues, representative tumor regions were selected from hematoxylin and eosin-stained slides. During tissue slide processing, xylene and a gradient of ethanol were used for deparaffinization, followed by antigen retrieval. Endogenous peroxidase in the tissue was blocked using a 0.3% hydrogen peroxide solution. Normal rabbit serum was used to incubate the tissue slides. The slides were then incubated with the primary anti-musashi-1 antibody for 24 hours. After incubation, the samples were reacted with biotin-labeled secondary antibodies and HRP-labeled streptavidin to form a visual signal. The 3,3’-diaminobenzidine substrate was used to produce a brown precipitate through HRP-catalyzed reaction, and musashi-1 staining distribution and intensity were observed under a microscope. Phosphate buffered saline was used as a negative control instead of the primary antibody to confirm no nonspecific staining reaction. For the immunohistochemical staining results of musashi-1, quantitative scoring was performed based on the staining intensity and the percentage of positive cells. Staining intensity was divided into four levels: 0 indicating no staining (negative); 1 indicating weak staining; 2 indicating moderate staining; and 3 indicating strong staining. Additionally, the percentage of positive cells was graded as follows: 0 indicating no positive cells (0%); 1 indicating 1%-30% positive cells; 2 indicating 31%-50% positive cells; and 3 indicating more than 50% positive cells. Finally, the staining intensity score was multiplied by the percentage score of positive cells to obtain the total score. Based on the score results, musashi-1 expression was classified into two groups: Samples with a total score of 0-2 were classified as “musashi-1 Low expression”, and samples with a total score greater than 2 were classified as “musashi-1 high expression”.
Treatment methods
The treatment strategy was selected based on the American Joint Committee on Cancer 8th edition tumor-node-metastasis staging system, combined with the patient’s specific conditions for individualized design. To accurately assess the clinical stage of ESCC patients, this study used a series of comprehensive imaging techniques, including esophagoscopy and biopsy, to obtain pathological information from the tumor tissue. Meanwhile, endoscopic ultrasound and chest and abdominal CT scans were used to further clarify the local invasion of the tumor and distant metastasis. For cases where conventional imaging methods were difficult to evaluate accurately, positron emission tomography-CT was used to obtain imaging information of systemic metabolic activity, helping to determine the presence of small metastatic lesions and optimize the treatment plan. The treatment process was divided into two stages: NCT and standard esophageal resection surgery. The specific treatment plan is as follows.
NCT: In the NCT phase, all patients received a two-cycle combination chemotherapy regimen consisting of paclitaxel and cisplatin. Each chemotherapy cycle lasted 21 days. On day 1, paclitaxel was administered intravenously at a dose of 135 mg/m2 over 1 hour, followed by cisplatin intravenous infusion on days 1 and 2 at a dose of 75 mg/m2 for 3 hours. This regimen aimed to reduce tumor volume, improve the success rate of surgical resection, and control the local invasiveness of the tumor preoperatively, thereby creating more favorable conditions for subsequent surgery.
Esophagectomy: All patients who underwent NCT received standard esophagectomy after the completion of chemotherapy. The specific surgical method and resection range were determined based on the tumor’s location, size, and clinical stage. For tumors located in the middle or lower thoracic esophagus, a two-stage esophagectomy was performed. The key to this surgery was to ensure that the proximal resection margin was at least 5 cm after esophagectomy, in order to reduce the risk of local recurrence postoperatively. For upper esophageal tumors, especially tumors located in the proximal thoracic esophagus, it might not be possible to meet the 5 cm resection margin requirement, so a three-stage esophagectomy was chosen to ensure an adequate safety margin, thereby reducing the likelihood of postoperative tumor recurrence. In addition, lymph node dissection was performed intraoperatively according to the specific conditions of the tumor and the extent of lymph node metastasis.
Evaluation criteria for treatment effect
After completing NCT, treatment efficacy was assessed according to the criteria for solid tumors[18]. Complete response (CR): All lesions disappear, and no new lesions are observed. Partial response (PR): The longest diameter of the lesion decreases by more than 30%. Stable disease (SD): The longest diameter of the lesion decreases by less than 30% or increases by less than 20%. Progressive disease (PD): The longest diameter of the lesion increases by 20% or more. These criteria must be sustained for more than 4 weeks to be determined. Disease control rate (DCR) = (CR + PR + SD cases/total cases) × 100%; overall response rate (ORR) = (CR + PR cases/total cases) × 100%. The tumor regression grade (TRG)[19] is assessed based on the degree of tumor regressive changes, divided into five levels: TRG1 (complete regression): No cancer cells remain on histological examination, the tumor completely disappears, and the esophageal wall is not invaded by cancer cells, indicating the best treatment outcome; TRG2 (partial regression): A small amount of residual cancer cells scattered on histological examination, the tumor has mostly regressed, and clinically shows significant remission; TRG3 (moderate regression): A large amount of residual cancer cells remains, but the malignancy of the tumor is reduced compared to before treatment, and the patient’s condition is under control; TRG4 (local regression with fibrosis): A large amount of tumor cells remain, with varying degrees of fibrosis, indicating that the tumor has not been completely controlled after treatment, and there is some tissue repair response; TRG5 (no regression): No significant regressive changes, and no significant reduction in cancer cells, indicating poor treatment effect, with the tumor almost unaffected by treatment.
Follow-up
After completing treatment, patients were followed up according to the prescribed schedule. The main goal of follow-up was to evaluate the patient’s overall survival (OS) and quality of life. The first follow-up visit occurred within 4 weeks after surgery, followed by monthly follow-ups during the first year, and quarterly follow-ups during the second year, until the patient’s death or the end of the study. Each follow-up required a series of standardized examinations, including: (1) Physical examination: A comprehensive physical condition assessment, particularly focusing on the recovery status after esophageal surgery, such as wound healing and nutritional status; (2) Gastroscopy and biopsy: Regular gastroscopy was performed to observe the healing process of the esophagus post-surgery, and biopsies were taken as needed to confirm whether there was tumor recurrence or new lesions; (3) Imaging examinations: Regular chest and abdominal CT scans and ultrasound were performed to assess the risk of tumor recurrence and other possible complications. These imaging examinations provided dynamic information on tumor development and organ function; and (4) Laboratory tests: Blood tests, such as tumor marker level detection, were conducted as required to assess the patient’s disease status during follow-up. OS was the primary survival prognosis indicator, referring to the time from the moment the patient underwent surgical treatment to the time of death or the last follow-up.
Statistical analysis
GraphPad Prism 8 was used for graphing software, and SPSS 25.0 was used for statistical analysis. Measurement data were presented as mean ± SD, and categorical data were expressed as n (%). The differences between two groups were compared using univariate analysis, χ2 test or Fisher’s exact test for categorical variables. For continuous data with normal distribution, a t-test was used. Continuous and multicategory categorical variables were converted into binary outcomes based on standard clinical or widely accepted thresholds. Kaplan-Meier curves were analyzed, and the log-rank test was used to determine patient survival to assess significance. Multivariate analysis using the Cox proportional hazards model was conducted to evaluate significant predictive factors. All confidence intervals (CI) were set at 95%. A P value of < 0.05 was considered statistically significant.
RESULTS
Comparison of clinical pathological parameters between groups A and B
There were significant differences between group A and group B in tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, lymphovascular invasion, and intraoperative bleeding (P < 0.05), as shown in Table 1.
Table 1 Comparison of clinical pathological parameters between groups A and B, n (%).
Group A (n = 30)
Group B (n = 44)
t/χ2
P value
Gender
-
-
0.313
0.575
Male
20 (66.67)
32 (72.73)
-
-
Female
10 (33.33)
12 (27.27)
-
-
Age (years)
61.54 ± 7.35
60.27 ± 7.99
0.693
0.490
BMI (kg/m2)
22.36 ± 3.18
23.15 ± 2.84
1.119
0.266
Tumor location
-
-
0.380
0.537
Upper segment
5 (16.67)
4 (9.09)
-
-
Middle segment
15 (50.00)
20 (45.45)
-
-
Lower segment
10 (33.33)
20 (45.45)
-
-
Maximum tumor diameter (cm)
4.61 ± 1.25
3.84 ± 1.19
2.677
0.009
T stage
-
-
11.929
< 0.001
T2
5 (16.67)
25 (56.82)
-
-
T3
13 (43.33)
12 (27.27)
-
-
T4a
12 (40.00)
7 (15.91)
-
-
N stage
-
-
9.207
0.002
N0
9 (30.00)
29 (65.91)
-
-
N1
11 (36.67)
10 (22.73)
-
-
N2
10 (33.33)
5 (11.36)
-
-
Clinical stage
-
-
14.519
< 0.001
II
5 (16.67)
27 (61.36)
-
-
III
19 (63.33)
12 (27.27)
-
-
IVa
6 (20.00)
5 (11.36)
-
-
Pathological grade
-
-
5.722
0.016
G1
5 (16.67)
19 (43.18)
-
-
G2
12 (40.00)
21 (47.73)
-
-
G3
13 (43.33)
4 (9.09)
-
-
Lymphovascular invasion
-
-
4.012
0.045
Present
18 (60.00)
16 (36.36)
-
-
Absent
12 (40.00)
28 (63.64)
-
-
Neural invasion
-
-
2.547
0.110
Present
12 (40.00)
10 (22.73)
-
-
Absent
18 (60.00)
34 (77.27)
-
-
Tumor infiltration depth
-
-
1.087
0.297
Submucosal
10 (33.33)
20 (45.45)
-
-
Muscular
12 (40.00)
16 (36.36)
-
-
Adventitia
8 (26.67)
8 (18.18)
-
-
History of thoracic/abdominal surgery
-
-
2.224
0.135
Present
10 (33.33)
8 (18.18)
-
-
Absent
20 (66.67)
36 (81.82)
-
-
Intraoperative bleeding
-
-
3.975
0.046
Present
15 (50.00)
12 (27.27)
-
-
Absent
15 (50.00)
32 (72.73)
-
-
Perioperative transfusion
-
-
3.535
0.060
Present
13 (43.33)
10 (22.73)
-
-
Absent
17 (56.67)
34 (77.27)
-
-
Postoperative complications
-
-
2.224
0.135
Present
10 (33.33)
8 (18.18)
-
-
Absent
20 (66.67)
36 (81.82)
-
-
Comparison of treatment efficacy between groups A and B
Among the 30 patients in group A, there were 0 cases of CR, 10 cases of PR, 16 cases of SD, and 4 cases of PD. Regarding TRG grading, there were 0 cases of TRG1, 6 cases of TRG2, 17 cases of TRG3, and 7 cases of TRG4 + 5. Among the 44 patients in group B, there were 11 cases of CR, 20 cases of PR, 13 cases of SD, and 0 cases of PD. Regarding TRG grading, there were 7 cases of TRG1, 18 cases of TRG2, 16 cases of TRG3, and 3 cases of TRG4 + 5. The DCR in group A (86.67%) was lower than that in group B (100.00%) (χ2 = 3.868, P = 0.049); the ORR in group A (33.33%) was lower than that in group B (70.45%) (χ2 = 9.948, P = 0.001), as shown in Figure 1. The proportion of TRG3 + 4 + 5 in group A (80.00%) was higher than that in group B (43.18%) (χ2 = 9.933, P = 0.001), as shown in Figure 2.
Figure 1 Comparison of clinical efficacy between groups A and B.
PR: Partial response; SD: Stable disease; PD: Progressive disease; CR: Complete response.
Figure 2 Comparison of tumor regression grade between groups A and B.
TRG: Tumor regression grade.
Analysis of factors related to patient prognosis
Univariate analysis showed that the maximum tumor diameter, T stage, N stage, clinical stage, pathological grade, and musashi-1 expression were all associated with patient prognosis (P < 0.05), as shown in Table 2. Significant variables from the univariate analysis were included in the multivariate Cox regression analysis model. The results indicated that T stage [hazard ratio (HR) = 1.82, 95%CI: 2.14-7.37], N stage (HR = 1.70, 95%CI: 1.12-2.36), clinical stage (HR = 2.08, 95%CI: 1.36-3.85), pathological grade (HR = 1.54, 95%CI: 1.07-2.41), and musashi-1 expression (HR = 2.72, 95%CI: 2.03-4.11) were independent risk factors affecting patient prognosis (P < 0.05), as shown in Table 3.
Table 2 Univariate analysis of factors affecting patient prognosis.
The impact of musashi-1 expression level on patient survival
Kaplan-Meier survival curves showed that the median OS for group A and group B were 17 months and 28 months, respectively. Log-rank analysis showed that the OS rate of group A was worse than that of group B (χ2 = 2.635, P = 0.033), as shown in Figure 3.
Figure 3 The impact of musashi-1 expression level on patient survival.
DISCUSSION
This study found that patients in group A (high musashi-1 expression) exhibited significantly worse clinical pathological features, such as maximum tumor diameter, T stage, N stage, clinical stage, pathological grade, lymphovascular invasion, and intraoperative bleeding. This suggests that high musashi-1 expression may be closely related to the malignancy of ESCC, further supporting its potential as a tumor progression marker. Previous studies have shown that musashi-1 is highly expressed in various types of tumors, and its expression level is closely related to tumor characteristics such as invasiveness, metastatic potential, and degree of differentiation. For example, the study by Lagadec et al[20] indicated that musashi-1 could maintain the self-renewal capacity of CSCs by activating the Notch signaling pathway. Kudinov et al[21] found that in colorectal cancer, musashi-1 promotes tumor stem cell proliferation and drug resistance by inhibiting the expression of the Numb protein. The results of this study further corroborate these findings. We hypothesize that musashi-1 may promote tumor malignancy by regulating the stem cell properties of tumor cells, leading to adverse clinical pathological features during treatment.
NCT is an important treatment modality for resectable ESCC, aimed at shrinking tumor volume, reducing postoperative complications, and improving surgical resection rates[22,23]. However, in some patients, despite receiving NCT, the treatment effects remain unsatisfactory. The results of this study show that high musashi-1 expression is closely associated with poor treatment outcomes. Specifically, patients in group A had significantly lower DCR (86.67% vs 100.00%, P = 0.049) and ORR (33.33% vs 70.45%, P = 0.001) compared to group B. Moreover, patients in group A exhibited poorer pathological treatment responses (TRG grading) (80.00% vs 43.18%, P = 0.001). These results suggest that high musashi-1 expression may be related to resistance to NCT and poor treatment outcomes. Previous related studies have shown that high musashi-1 expression is typically associated with tumor cell self-renewal, proliferation, and drug resistance[24-26]. We speculate that musashi-1 may enhance the proliferative and migratory capacities of tumor cells by promoting their stem cell-like characteristics, thereby inducing resistance to chemotherapy drugs and resulting in poor treatment effects. This finding is important for guiding clinicians in more accurately assessing patient treatment responses and adjusting treatment plans. Although this study primarily focuses on the role of musashi-1 in NCT, it should also consider the potential role of musashi-1 in other therapeutic strategies, particularly in the context of immunotherapy. With the widespread use of immune checkpoint inhibitors, immunotherapy has become a standard treatment for metastatic ESCC. Studies have shown that tumor cells evade host immune surveillance through various mechanisms, and musashi-1, as a stem cell-related protein, may play a crucial role in tumor immune evasion[27]. Experimental studies have indicated that musashi-1 not only participates in tumor initiation and progression but may also alter the immune microenvironment, affecting the infiltration and function of immune cells, thereby enhancing the tumor cell’s immune evasion capability[28]. This finding provides a new perspective on the role of musashi-1 in immunotherapy. Future research could explore the combination of musashi-1 with immunotherapy to evaluate whether it can enhance treatment efficacy, especially in patients who are resistant to immune checkpoint inhibitors.
This study further evaluated the relationship between musashi-1 expression and patient survival prognosis. Kaplan-Meier survival analysis showed that the median OS of patients in group A was significantly lower than that of group B (17 months vs 28 months, P = 0.033). Multivariate Cox regression analysis further indicated that high musashi-1 expression was an independent risk factor affecting patient prognosis (P < 0.05). These results are consistent with previous studies on musashi-1 as a prognostic marker in other tumor types[29-31]. High musashi-1 expression may promote tumor cell invasion, metastasis, and drug resistance, leading to tumor recurrence and metastasis in patients, which in turn shortens their survival[32,33]. The survival analysis results of this study provide strong evidence for the potential use of musashi-1 as a prognostic marker for ESCC patients. The findings suggest that high musashi-1 expression is not only related to the malignancy of tumors but also may be one of the key mechanisms for the development of drug resistance, tumor recurrence, and metastasis, making it a promising biomarker for evaluating the effectiveness of NCT and prognosis in ESCC patients. Regarding the relationship between musashi-1 and chemotherapy resistance, although we have already found that high expression of musashi-1 is closely associated with drug resistance and poor treatment response in this study, its role in other treatment types, especially in CRT, remains underexplored. Given that musashi-1 may significantly influence tumor cell growth and differentiation through its regulated signaling pathways (such as Notch, Wnt, mammalian target of rapamycin, etc.), future research should further investigate its role in chemoradiotherapy. Chemoradiotherapy may interact with musashi-1 through more complex mechanisms, and thus studying the expression of musashi-1 in this treatment modality and its prognostic value could help reveal a more comprehensive clinical application potential.
Although the findings of this study have certain clinical implications, several limitations should be acknowledged. First, this is a single-center retrospective study with a relatively small sample size, which may introduce selection bias, such as uneven baseline characteristics among patients; thus, the results should be interpreted with caution. Second, the specific molecular pathways involved in musashi-1-mediated drug resistance remain unclear and require further validation through cellular and animal experiments. Therefore, future research is recommended in the following areas: (1) Expanding the sample size and conducting multicenter prospective studies to enhance the robustness and generalizability of the findings; (2) Employing multi-omics approaches, such as transcriptomics and proteomics, to systematically analyze the molecular networks and signaling pathways regulated by musashi-1; and (3) Further exploring the synergistic effects between musashi-1 and other CSC markers (e.g., CD44, ALDH1) to construct a more comprehensive tumor stemness profile and strengthen the biological basis for individualized treatment strategies.
In addition, future studies should also focus on the feasibility of promoting musashi-1 detection methods in clinical settings. Currently, musashi-1 detection mainly relies on IHC, which offers advantages such as operational simplicity and clear tissue origin. However, for broader multicenter application, standardized testing procedures and unified interpretation criteria are needed to ensure the accuracy and reproducibility of results. To facilitate its routine clinical use, it is necessary to further evaluate the stability and representativeness of musashi-1 expression in various tissue samples, such as preoperative biopsies and liquid biopsies.
On the other hand, as a stem cell-related protein, musashi-1 plays a critical role in tumor development and drug resistance, suggesting its potential as a therapeutic target. Recent studies have attempted to develop small molecule inhibitors targeting musashi-1, which have preliminarily shown the ability to reduce tumor cell stemness, suppress proliferation, and enhance sensitivity to chemotherapeutic agents. Furthermore, combining musashi-1 inhibition with immunotherapy or conventional chemotherapy may serve as an effective strategy to improve treatment responses. Therefore, future research could explore the clinical translational potential of musashi-1-targeted interventions from multiple dimensions, including drug screening, mechanistic studies, and animal experiments.
CONCLUSION
In summary, this study systematically explored the expression of musashi-1 in resectable ESCC patients and its relationship with NCT efficacy and survival prognosis. The results indicate that musashi-1 expression is closely related to treatment outcomes, prognosis, and survival in ESCC patients. It holds potential as a biomarker for evaluating treatment efficacy and prognosis in ESCC patients and provides a theoretical basis for the development of novel therapeutic strategies targeting CSCs. Future research should further verify the clinical value of musashi-1 and explore its feasibility as a therapeutic target.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Cell and tissue engineering
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade B, Grade B
Novelty: Grade B, Grade B, Grade C, Grade C
Creativity or Innovation: Grade B, Grade B, Grade C, Grade C
Scientific Significance: Grade B, Grade B, Grade C, Grade C
P-Reviewer: Cao YS; Liu H; Wen L S-Editor: Wang JJ L-Editor: A P-Editor: Zhang YL
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