FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer
Abstract Objective A significant proportion of patients can not benefit from neoadjuvant chemotherapy (NCT) due to drug resistance. Cancer-associated fibroblasts (CAFs) influence many biological behaviours of tumors, including chemo-resistance. This study aims to explore whether CAFs expressing FAP,...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11011-0 |
| _version_ | 1827928669566271488 |
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| author | Zehua Zhao Yanmei Zhu |
| author_facet | Zehua Zhao Yanmei Zhu |
| author_sort | Zehua Zhao |
| collection | DOAJ |
| description | Abstract Objective A significant proportion of patients can not benefit from neoadjuvant chemotherapy (NCT) due to drug resistance. Cancer-associated fibroblasts (CAFs) influence many biological behaviours of tumors, including chemo-resistance. This study aims to explore whether CAFs expressing FAP, CD10, and GPR77 affect the efficacy of NCT and the prognosis of patients with gastric cancer, and its mechanism. Methods One hundred seventy-one patients with locally progressive gastric adenocarcinoma who had undergone NCT and radical surgery were collected. Immunohistochemistry was used to detect the expression of FAP, CD10, and GPR77 in CAFs; the EMT markers (N-cadherin, Snail1, and Twist1) and the CSC markers (ALDH1, CD44, and LGR5) in gastric cancer cells. The χ2 test was used to analyze the relationship between the expression of CAF, EMT, and CSC markers and the clinicopathological factors, as well as the relationship between CAF markers and EMT, and CSC markers. Logistic regression and Cox risk regression were used to analyze the relationship between the expression of CAF, EMT, and CSC markers and TRG grading and OS; Kaplan-Meier analysis was used for survival analysis and plotting the curves. Results The expression of CAF markers FAP, CD10, and GPR77 was closely associated with that of EMT markers; FAP and CD10 were closely related to CSC markers. In the univariate analysis of pathological response, CAF markers (FAP, CD10, GPR77), EMT markers (N-cadherin, Snail1, Twist1), and CSC markers (ALDH1, LGR5, CD44), were all closely associated with pathological response (all p < 0.05). Only Twist1 was an independent factor affecting pathological response in multifactorial analysis (p = 0.001). In a univariate analysis of OS, expression of FAP and CD10 in CAF, as well as expression of EMT biomarkers (N-cadherin, Snail1), were significant factors influencing patient prognosis (all p < 0.05). Multifactorial analysis revealed N-cadherin (p = 0.032) and Snail1 (p = 0.028), as independent prognostic factors affecting OS. Conclusion FAP, CD10, and GPR77 labeled CAF subgroup may lead to NCT resistance and poor prognosis by inducing EMT and CSC of gastric cancer cells in locally advanced gastric cancer patients. |
| first_indexed | 2024-03-13T06:10:59Z |
| format | Article |
| id | doaj.art-f75dab85990f418a81671decdc5afad6 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-13T06:10:59Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f75dab85990f418a81671decdc5afad62023-06-11T11:16:40ZengBMCBMC Cancer1471-24072023-06-0123111510.1186/s12885-023-11011-0FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancerZehua Zhao0Yanmei Zhu1Department of Pathology, Dadong District, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University)Department of Pathology, Dadong District, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University)Abstract Objective A significant proportion of patients can not benefit from neoadjuvant chemotherapy (NCT) due to drug resistance. Cancer-associated fibroblasts (CAFs) influence many biological behaviours of tumors, including chemo-resistance. This study aims to explore whether CAFs expressing FAP, CD10, and GPR77 affect the efficacy of NCT and the prognosis of patients with gastric cancer, and its mechanism. Methods One hundred seventy-one patients with locally progressive gastric adenocarcinoma who had undergone NCT and radical surgery were collected. Immunohistochemistry was used to detect the expression of FAP, CD10, and GPR77 in CAFs; the EMT markers (N-cadherin, Snail1, and Twist1) and the CSC markers (ALDH1, CD44, and LGR5) in gastric cancer cells. The χ2 test was used to analyze the relationship between the expression of CAF, EMT, and CSC markers and the clinicopathological factors, as well as the relationship between CAF markers and EMT, and CSC markers. Logistic regression and Cox risk regression were used to analyze the relationship between the expression of CAF, EMT, and CSC markers and TRG grading and OS; Kaplan-Meier analysis was used for survival analysis and plotting the curves. Results The expression of CAF markers FAP, CD10, and GPR77 was closely associated with that of EMT markers; FAP and CD10 were closely related to CSC markers. In the univariate analysis of pathological response, CAF markers (FAP, CD10, GPR77), EMT markers (N-cadherin, Snail1, Twist1), and CSC markers (ALDH1, LGR5, CD44), were all closely associated with pathological response (all p < 0.05). Only Twist1 was an independent factor affecting pathological response in multifactorial analysis (p = 0.001). In a univariate analysis of OS, expression of FAP and CD10 in CAF, as well as expression of EMT biomarkers (N-cadherin, Snail1), were significant factors influencing patient prognosis (all p < 0.05). Multifactorial analysis revealed N-cadherin (p = 0.032) and Snail1 (p = 0.028), as independent prognostic factors affecting OS. Conclusion FAP, CD10, and GPR77 labeled CAF subgroup may lead to NCT resistance and poor prognosis by inducing EMT and CSC of gastric cancer cells in locally advanced gastric cancer patients.https://doi.org/10.1186/s12885-023-11011-0CAFChemo-resistanceEMTCSCGastric cancer |
| spellingShingle | Zehua Zhao Yanmei Zhu FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer BMC Cancer CAF Chemo-resistance EMT CSC Gastric cancer |
| title | FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer |
| title_full | FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer |
| title_fullStr | FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer |
| title_full_unstemmed | FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer |
| title_short | FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer |
| title_sort | fap cd10 and gpr77 labeled cafs cause neoadjuvant chemotherapy resistance by inducing emt and csc in gastric cancer |
| topic | CAF Chemo-resistance EMT CSC Gastric cancer |
| url | https://doi.org/10.1186/s12885-023-11011-0 |
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